Experiments were carried out to examine relationships between alveolarmacrophage maturity and amounts of tissue factor (Clotting Factor Ⅲ)inthese cells under physiologic conditions and during immunologically inducedpneumonitis.Using discontinuous density gradient centrifugation,alveolarmacrophages from healthy rabbits were rapidly isolated into five subpop-ulations at different stages of maturation,as demonstrated by morphologicand morphometric evaluation.Very large amounts of tissue factor activitywere found in fully mature cells that were purified in the lowest densitysubpopulation and assayed without preliminary in vitro stimulation orculture.In the remaining four subpopulations of increasing density,amounts oftissue factor were found to progressively diminish in direct correlation withdeclines of cell maturity.These differences at mean levels were as great as35-fold.In addition,blood monocytes had <1/219 and<1/6 of the activityof the fully mature and the least mature subpopulations,respectively.After16 h culture of the five isolated subpopulations in the absence of lymphok-ines or of significant numbers of lymphocytes,tissue factor activity increa-sed in inverse correlation with the preincubation stage of cell maturity(2,387)and 109% in the least mature and most mature subpopulations,resp-ectively).These increases required protein synthesis and were accompaniedby morphologic and morphometric changes which indicated cellularmaturation during the period of tissue factor activity generation in vitro,thus further demonstrating relationships between macrophage maturity andtissue factor content.In additional experiments,direct correlations between cell maturity and tissue factor activity content were also found in activatedalveolar macrophage populations from rabbits with Bacillus CalmetteGuering (BCG)-induced granulomatous pneumonitis.However,as comparedwith controls,the BCG populations had increased total amounts of tissuefactor activity due to the presence of large numbers of mature alweolarmacrophage forms that had high levels of the procoagulant.Thus,tissuefactor activity in alveolar macrophages is a marker of cellular maturationin vivo and in vitro.Increased amounts of this initiator of the extrinsicclotting pathway,as found in alveolar macrophage populations from animalswith granulomatous pneumonitis induced by BCG hypersensitivity,suggestthat alveolar macrophage tissue factor may contribute to the pathology ofimmune lung diseases. Experiments were carried to examine relationships between alveolar macrophage maturity and amounts of tissue factor (Clotting Factor III) inthese cells under physiologic conditions and during immunologically induced pneumonitis. Using discontinuous density gradient centrifugation, alveolarmacrophages from healthy rabbits were rapidly isolated into five subpop-ulations at different stages of maturation, as demonstrated by morphologic and morphometric evaluation. Very large amounts of tissue factor activity were found in fully mature cells that were purified in the lowest densitysubpopulation and assayed without preliminary in vitro stimulation or culture. the remaining four subpopulations of increasing density, amounts of tissue factor were found to progressively diminish in direct correlation withdeclines of cell maturity.These differences at mean levels were as great as 35 -fold.In addition, blood monocytes had <1/219 and <1/6 of the activity of the fully mature and the least mature subpopulatio ns, respectively. After 16 h culture of the five isolated subpopulations in the absence of lymphok-ines or of significant numbers of lymphocytes, tissue factor activity increa-sed in inverse correlation with the preincubation stage of cell maturity (2,387) and 109% in the least mature and most mature subpopulations, resp-ectively). These increases required protein synthesis and were accompanied by morphologic and morphometric changes which indicated cellular maturation during the period of tissue factor activity generation in vitro, thus further demonstrating relationships between macrophage maturity and factor content content. additional experiments, direct correlations between cell maturity and tissue factor activity content were also found in activatedalveolar macrophage populations from rabbits with Bacillus Calmette Guering (BCG) -induced granulomatous pneumonitis. Host, as compared with controls, the BCG populations had increased total amount of tissue factor activity activity due to the presence of lar ge numbers of mature alweolarmacrophage forms that had high levels of the procoagulant. Thus, tissue factor activity in alveolar macrophages is a marker of cellular maturation in vivo and in vitro. Increased amounts of this initiator of the extrinsic moting pathway, as found in alveolar macrophage populations from animalswith granulomatous pneumonitis induced by BCG hypersensitivity, suggestthat alveolar macrophage tissue factor may contribute to the pathology ofimmune lung diseases.