Diastereomeric N,”-dialkyl- 1,2-bis(hydroxyphenyl)ethylenediamines (5) were synthesized and tested for their affinity for the estradiol receptor. Only the (&)-1,2-bis(4-hydroxyphenyl)ethylenediamines with the alkyl groups C3H7 [ (&)-5c, K, = 1.1 X lo6)],C ,H9 [(&)-5e,K=, 3.6 X lo6], and CSHll [(*)-5h, K, = 2.2 X lo6] showed a marked affinity, which is mainly due to the (+) enantiomers [e.g., (+)-5e, K, = 2.1 X lo7]. No enhancement of affinity by cyclization to imidazolidines [e.g., (f)-trans-7a, K, = 1.2 X lo7] was observed. These compounds [e.g., (&)-, (+)-, and (-)-5e], which did not produce any uterine response in the mouse, were able to inhibit weakly the growth of the DMBA-induced mammary carcinoma of the rat. The inhibitory effect of (f)-5e against MCF-7 cells, which can be overcome by hexestrol, makes a direct antiestrogenic mode of action probable, since general cytotoxic effects and a central action could be ruled out.