AIM Human dermal fibroblasts in a dermal tissue model show reduced proliferation or cell-matrix contact inhibition (CMI), distinct from cell-cell contact inhibition (CCI) at confluent.Epidermal growth factor (EGF) reinitiate the growth of CCI cells,while it can not stimulate CMI cell proliferation though EGF can bind with the fibroblasts.Saikosaponin bl in combination with EGF can reinitiate the proliferation of CMI fibroblasts.The present study compares the effects of saikosapnin bl on collagen synthesis by CMI fibroblasts with that by CCI fibroblasts.METHODS Isotope labeled proteins synthesized are classified into collagen and noncollagen with bacterial collagenase treatment.RESULTS EGF binding to CCI ceils in the presence of saikosaponin bl indicated that EGFR numbers increased without changing the affinities, which eventually promotes EGFR signaling.Ascorbic acid stimulated CCI fibroblasts to synthesize collagen, while it did not affect CMI fibroblasts.The combination of saikosaponin bl and EGF reduced collagen production by CCI fibroblasts.It further decreased collagen synthesis by CMI fibroblasts.CONCLUSION The effect of saikosaponin bl on CMI fibroblasts is most conspicuous with EGF in repressing collagen synthesis as well as in growth stimulation presumably through enhancing EGFR signaling.