17-beta-Estradiol (10 nmol per 200 microl acetone) applied topically twice weekly to the clipped dorsal surface of C57BL/6 or C3H female mouse skin prevented hair growth, as previously described in the CD-1 mouse strain. Twice weekly topical application of the estrogen receptor antagonist, ICI 182 780 (10nmol per 200microl acetone), induced the telogenanagen transition and produced early pigmentation appearance in skin and hair growth in C57BL/6 and C3H female mice. Whereas twice weekly topical application of 10nmol 17-beta-estradiol blocked hair growth, the intraperitoneal administration of this dose twice weekly did not block hair growth, suggesting a direct cutaneous effect of 17-beta-estradiol. We also evaluated the effect of 17-alpha-estradiol, 17-beta-estradiol, and ICI 182 780 on hair growth in male mice. As observed in female mice, 17-beta-estradiol was a potent inhibitor of hair growth and ICI 182 780 stimulated hair growth; however, unlike the results previously observed in female mice, 17-alpha-estradiol was a potent inhibitor of hair growth in male mice. These results demonstrate that (i) the route of administration of 17-beta-estradiol is critical for its ability to block hair growth; (ii) C57BL/6 and C3H mice, two commonly employed mouse strains for hair growth studies, responded to 17-beta-estradiol and ICI 182 780 in a manner similar to that described in CD-1 mice; and (iii) the hair follicles of male and female mice respond similarly to 17-beta-estradiol and ICI 182 780, but display striking sex differences in the response to 17-alpha-estradiol on hair growth.