Ethyl ether extracts derived from coffee were tested for in vitro estrogenic and in vivo uterotropic activities. Coffee extracts, unlike tea and cocoa, were found to actively compete with 17 beta-estradiol for uterine cytosol binding sites. The biologically active fractions possessed an unique ultraviolet absorbance spectrum that excluded them from containing flavonoid, coumestan, or resorcyclic acid lactone constituents. Coffee extracts administered to immature female mice for 3 d in feeding studies displayed significant (p less than 0.05) uterotropic responses, which were similar to results obtained in mice treated with a standard 17 beta-estradiol dose. Additional studies in mice disclosed that coffee extracts did not reduce the uterotropic effect normally induced by 17 beta-estradiol when administered simultaneously with estradiol. The complete estrogenic effects of coffee constituents, coupled with their failure to inhibit a biological response evoked by estradiol, strongly suggest that coffee contains constituent(s) that are weakly estrogenic.