The effects of Gly-His-Lys-Cu and of three synthetic analogues (I, II and III) on wound healing of the guinea-pig dorsal skin, as well as on cultured fibroblasts, were examined. Gly-His-Lys-Cu and peptide I-Cu were tested in vivo. Hydroxyproline, proteins, DNA and semicarbazide-sensitive amine oxidase, with a high affinity for benzylamine, were measured, and the histology of the wounds was observed after staining with hematoxylin/eosin. Another set of wounds was treated in parallel with equivalent amounts of copper acetate. Gly-His-Lys-Cu and the analogues caused a decrease of the activity of semicarbazide-sensitive amine oxidase, with a high affinity for benzylamine, 4-8 days after surgery, followed by an increase on day 11 that was higher than in the control group. No significant difference was found between the two peptides. A slower reorganization of the skin and a delayed activation of fibroblasts are the main effects observed with these peptides-Cu complexes. Preliminary studies on cultured fibroblasts were monitored to see whether these peptides had a direct effect on fibroblasts. The products studied at a concentration of 10(-7) M, decreased cell reproduction and increased collagen expression.