Administration of 13-cis-retinoic acid subcutaneously to mature male hamsters produced a marked decrease in the size of the sebaceous glands of the flank organ, without diminution of other hormonally dependent structures of the flank organs. Subcutaneous administration of 13-cis-retinoic acid to female hamsters treated simultaneously with injections of testosterone enanthate prevented the androgen-induced growth of the flank organ sebaceous glands but did not prevent the growth of other hormonally dependent structures such as the dermal pigment cells and large pigmented hair follicles. The sebaceous gland progressively decreased during 3 weeks of treatment and the effect persisted at least 3 weeks after cessation of treatment but was completely reversed by 6 mos after treatment. In vitro studies of testosterone metabolism by hamster flank organ indicated the lack of inhibition of 5a-reduction by 13-cis-retinoic acid. It seems likely that systemically administered 13-cis-retinoic acid, unlike antiandrogens, exerts a specific extrahormonal effect on the sebaceous glands of the hamster flank organ without affecting other androgen dependent cells.