Using highly stabilized catecholestrogen preparations-ascorbic acid added to the free alcohols or benzoic acid derivatives — 2- and 4-hydroxyestrogens were tested in simple, clearly defined animal models: As index for the peripheral action the influence on vaginal opening and uterus weight gain was monitored after continuous s.c. administration for 6 days (minipumps) in immature intact rats resulting in a relative estrogenic potency (estradiol = 100%) of 70–100% for 4-hydroxyestradiol and less than 30% for 2-hydroxyestradiol. As index for the central action LH levels were measured in adult ovx rats leading to the same relations in the relative potencies. As index for both central and peripheral actions LH levels and the formation of corpora lutea were investigated in animals with an intact but prepubertal feed-back loop, i.e. in 25-day-old immature rats. 4-Hydroxyestradiol in this model clearly triggered LH surges and induced ovulations, its potency being in the same range as that of estradiol. 2-Hydroxyestradiol, in comparable doses, again showed no significant effect. Finally, female immature animals known to ovulate 3 days after PMS injection were treated concomitantly with either primary or catecholestrogen-antibody preparations. Whereas the primary estrogen antibody significantly blocked ovulation, the 2- and 4-hydroxyestrogen antibodies were ineffective. If, however, PMS and estrogen-antibody treated animals were supplemented with 4-hydroxyestrogens, ovulations could be restored. Thereby, it was inferred that peripheral 4-hydroxyestrogens, though not essential for the physiology of reproduction, can completely replace the physiologically essential peripheral estradiol at central target si