The antinociception of cannabinoid has generated a lot of interest in the past years[1].Hemopressin was reported as the first peptide ligand of the cannabinoid receptors[2].The pharmacological activities of hemopressin and its related peptide were investigated in our recent studies[3-5].However the development of cross-tolerance among these peptides is less clear.In the present study,hemopressin dose-dependently produced antinociception after supraspinal administration in the radiant heat tail-flick test.Furthermore,the development of antinociceptive tolerance to hemopressin,VD-hemopressin(α)and WIN55,212-2,and cross-tolerance among these cannabinoids were investigated in mice.