We have previously reported that mast cells (MC) stimulate 3T3 fibroblast migration and proliferation into an in vitro model of wound obtained by producing in a confluent 3T3 monolayer, a midline cut and by scraping the cells from half of the monolayer. The purpose of the present study was to determine the contribution of mast cell-derived histamine to this MC increasing effect. Histamine levels in supernatants of MC/3T3 cultures unactivated or activated with either compound 48/80 or anti-IgE antibodies (10 min) did not correlate to the degree of fibroblast migration and proliferation into the wound space (42h). Various concentrations of histamine were added to 3T3 fibroblast monolayers in the absence of cocultured MC, and fibroblasts beyond the wound line were counted (42 h). Addition of 100 ng/ml histamine had the highest stimulating effect on fibroblast numbers. This effect was abrogated by the addition of cimetidine (an H-2 antagonist). Addition of cimetidine to unactivated MC/3T3 cultures did not affect the increasing activity of MC presence on the wounded monolayer, although it diminished the enhancing effect obtained after MC activation with compound 48/80. These results indicate that histamine is partially responsible for the mast cell enhancing effect on fibroblast migration and proliferation in an in vitro model of wound.