Cloned human MCF-7 breast tumor cells were prevented from proliferating when grown in charcoal-dextran stripped human female serum (CDFHS)-supplemented media (40% and 10%); this inhibition was maximally cancelled by estradiol-17, cisTamoxifen, and Metabolite E, whereas Tamoxifen, N-desmethylTamoxifen and Metabolite Y only partially blocked the inhibitory effect of CDFHS. The efficiency of this reversing effect was estradiol-17 greater than Metabolite E greater than cisTAM greater than OHTAM greater than TAM = Metabolite Y. CDFHS at 2% allowed for near maximal cell yield; estradiol-17 at concentrations above 3 X 10(-10) M inhibited cell proliferation whereas at lower concentrations was ineffective. All the triphenylethylenes tested at 2% CDFHS were toxic above 3 X 10(-7) M; beyond these concentrations, these drugs did not significantly affect the cell yield. The proliferative properties of E2 and these triphenylethylenes do not directly correlate with their binding affinities to the intracellular estrophilins. Finally, the control of the proliferation of C7MCF7-173 cells appears to be affected by the interaction among a) estradiol-17 or the triphenylethylenes, b) a specific blood-borne inhibitor of the proliferation of estrogen-sensitive cells (estrocolyones), and c) an inhibitor "receptor"-like structure in these target cells.