The effect of retinoic acid (RA) on testosterone metabolism was examined in a prostatic cancer cell line of human origin, PC-3. In cells growing as monolayers as well as in cell homogenates RA causes a dose-dependent inhibition of the 5 alpha-reductase activity, thus preventing the conversion of testosterone into its hormonally active metabolite, dihydrotestosterone. Fifty per cent inhibition of the enzyme activity occurred at an RA concentration of 2 x 10(-5)M. The pattern of inhibition was that of a non-competitive inhibitor. However, when incubations were performed in the presence of varying amounts of NADPH, it turned out that RA exerts its effect by competitive inhibition of the cofactor action. Although the severe toxicity of RA precludes its systemic use as a 5 alpha-reductase inhibitory drug in humans, the possible anti-androgenic effect of other, less toxic, retinoids should be investigated.