The activation of the autogenous mast cells (MCs) in situ in intact mesenterial windows was elicited by the intraperitoneal injection of the MC secretagogue Compound 48/80 over a period of 1, 3 and 5 days in Sprague-Dawley rats and in C57 BL/6 and CBA/Ca mice. As a probe of MC secretion, the release of histamine was quantified fluorometrically at predetermined intervals during the treatment. Fourteen days after the start of the treatment, the angiogenic response was quantified histologically as the number of vessel profiles per unit length of mesenteric window. Both the MC-activating and the angiogenic effect of the 48/80-treatment was greater in the rats than in the mice. The occurrence of MC-mediated angiogenesis in the mouse is demonstrated here for the first time. In the rat, 48/80-induced MC mediated angiogenesis increased in a distinctly dose-dependent manner. Two daily doses of 48/80 was the most efficient angiogenic protocol tested; a single day's treatment increased the number of vessels almost fivefold. The remarkable potency of the angiogenic reaction following MC secretion supports our previous notion that MC-mediated angiogenesis may have therapeutic implications in poorly vascularized tissues.