In vivo, topical minoxidil therapy is associated with changes in the follicular epithelium, tissue and blood lymphocyte populations, lymphocyte blastogenic response to mitogens, and perifollicular vasculature. Biopsy specimens taken from areas of terminal hair regrowth show a dose-dependent increase in hair follicle length, a decrease in tissue lymphocyte populations associated with a simultaneous increase in peripheral blood lymphocyte counts, and reopening of previously closed lumina of perifollicular vessels. Responder lymphocytes show pretreatment-increased concanavalin A and phytohemagglutinin-induced blastogenesis, which decrease toward control values after treatment. In vitro, at concentrations approximating the range of tissue levels in patients treated topically with the 5% solution, minoxidil affects both epithelial cells and lymphocytes in tissue culture. Cultured murine epithelial cells show increased cell proliferation and delayed senescence. Cultured human lymphocytes show suppression of mitogen-induced blast transformation. Differential effects on responder, nonresponder, and control lymphocytes are seen. Minoxidil may induce hair regrowth in alopecia areata by a synergistic stimulatory effect on follicular epithelium and a suppressive effect on lymphocyte-mediated immunologic phenomena. A contributing role for its vasodilatory properties must also be considered.