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Binding of [³H]testosterone and 5-dihydro[³H]testosterone ([³H]DHT) to specific androgen-receptor sites of 5-reductase-deficient human genital skin fibroblasts (five cell-lines) was studied in the intact cultured cells at 37 °C. Under the conditions of the experiments, conversion of [³H]testosterone into [³H]DHT was negligible. Both steroids bound to the same set of high-affinity saturable sites in cytoplasmic and nuclear fractions of the cells. Unlabelled testosterone, DHT and methyltrienolone competed effectively with the labelled steroids. Progesterone and oestradiol were weaker competitors; cortisol did not compete. The dissociation constant (K_d) for high-affinity complexes with [³H]testosterone (0·44 ± 0·035 nmol/l) was higher than that for [³H]DHT complexes (0·20 ± 0·090 nmol/l). Unlabelled DHT was more effective than unlabelled testosterone in competing with either radioactive steroid. Complexes of [³H]DHT and receptor dissociated more slowly than [³H]testosterone-receptor complexes and [³H]DHT bound more extensively to low-affinity non-saturable sites in fibroblasts. As judged by competition with the radioactive androgens, progesterone bound to the androgen receptor with a K_d of about 7 nmol/l. 5-Pregnane-3,20-dione had an approximately fivefold lower affinity than progesterone for androgen receptors; 3/β- or 20-reduction lowered its affinity further. It is suggested that in 5-reductase deficiency in man, progesterone in amniotic fluid and blood could effectively inhibit testosterone binding to androgen receptors in the male embryonic external genitalia. One function of the high levels of 5-reductase activity normally found in embryonic external genitalia and urogenital sinus may be to protect these tissues from the potentially antiandrogenic action of progesterone.