We have examined the possibility that an involvement in hair growth regulation is one of the still obscure physiological roles of mast cells (MC) in normal skin. Using the murine hair cycle as a model, we first studied the number, localization, and granulation status of skin MC during the hair cycle of C 57 BL-6 mice. Shortly after the induction of hair growth (anagen) in the back skin of mice with resting (telogen) follicles, a sharp decline in the number of Giemsa-stainable MC was detected by morphometry. This was evident in depilation-induced, pharmacologically induced, and spontaneous anagen. By light and electron microscopy, the anagen-associated decline was correlated with the occurrence of substantial MC degranulation. In vivo, the IgE- independent MC secretagogues, compound 48/80 and ACTH, induced anagen in mouse telogen follicles after intracutaneous administration, while inhibitors of mast cell degranulation (cromoglycate, tiacrilast) and antagonists of selected MC products (clemastin, ranitidin, ketanserin) significantly retarded the induced development of anagen follicles in these mice. It is suggested that MC act via their secretory products as stimulators of anagen development in mice and that the murine hair cycle is an excellent model for studying growth regulatory functions of MC in developmentally regulated systems. © 1994 by Academic Press, Inc.