A number of 2-phenylindole derivatives with one hydroxy group in the meta or para position of the phenyl ring and a second one in position 5, 6, or 7 of the indole nucleus were synthesized. In addition, different alkyl groups were introduced into positions 1 and 3 of the heterocycle. The influence of these structural variations on the binding affinity for the calf uterine estrogen receptor was studied. A prerequisite for the binding is the presence of an alkyl group at the nitrogen. Favorable are a hydroxy group located in the para position of the phenyl ring and short alkyl chains both in position 1 and 3 of the indole. The highest relative binding affinity (RBA) values (e.g., 33 for 20b, 21 for 24b, 23 for 35b) are close to that of hexestrol (RBA = 25, estradiol = 100). Depending on the positions of the oxygen functions and size of the alkyl residues, the indole derivatives behaved as strong estrogens (20c, 24c, 35c) or impeded estrogens with antagonistic activity (23c, 29c, 30c, 31c, 40c, 44c) in the immature mouse. Some of these derivatives (20c, 23c, 24c, 29c, 30c, 31c) were tested for their inhibitory effect on dimethylbenzanthracene-induced hormone-dependent mammary tumors of the rat. Both types exhibited a strong growth inhibition with a reduction of the average tumor area at appropriate dosage. A mode of action involving the estrogen receptor system is assumed.