Δ5-Androstene-3β17β-diol (Adiol), in a dosage of 1000 μg/24 h injected ip into immature female Wistar rats (21-23 days old), induced 72 h after the injection the same elevations of uterine weight, cytosol protein, nuclear DNA, cytosol estrogen and progesterone receptors, and nuclear estrogen receptor levels as did 17β-estradiol (E2) in a dosage of 2.5 μg/24 h. Adiol appeared to translocate the estrogen receptor and induce the synthesis of estrogen and progesterone cytosol receptors in a manner almost identical to that of E2. Studies on the metabolism of tritiated Adiol ruled out the possibility that the estrogenic effects of Adiol might be mediated by conversion to E2. Small doses of Adiol (100 μg), which alone did not result in estrogenic effects, enhanced the effect of 2.5 μg E2 on uterine weight and progesterone receptor levels, whereas a dosage of 100 Hg dihydrotestosterone neither enhanced nor inhibited the uterine growth induced by 2.5 μg E2. A role for the androgen receptor in the synergism between Adiol and E2, therefore, appears to be ruled out. When Adiol in a dosage of 1000 μg was administered together with 2.5 μg E2, there was no important difference compared to either steroid alone up to 6 h. Thereafter, a very pronounced and prolonged secondary wave of translocation of the E2 receptor to the nucleus occurred which can explain the synergism between E2 and Adiol that became apparent in the same time interval. This secondary wave of translocation is most likely related to the persistent presence of both Adiol and E2 at the time of replenishment of the cytosol receptor (3-6 h after the injection). It is concluded that Δ5-androstene-3β17β-diol acts in the immature rat uterus like a fully potent estrogen with a complete lack of antiestrogenic effects. In this respect it differs from androgens like testosterone and dihydrotestosterone which can display both estrogenic and antiestrogenic activities.