The biliary excretion of diethylstilbestrol in the bile fistula rhesus monkey was investigated during exogenous taurocholate- and taurodehydrocholate-induced choleresis. Following intravenous administration, 36% of the dose was excreted into the bile (as diethylstilbestrol monoglucuronide) and 53% in the urine (as diethylstilbestrol monoglucuronide plus more polar unidentified metabolites). During the steady-state infusion of diethylstilbestrol, with taurocholate-induced choleresis, a bile flow dependent transport for the biliary excretion of diethylstilbestrol monoglucuronide was observed. Evidence for carrier-mediated transport of this metabolite was a bile-to-blood concentration ratio which ranged from 228 to 279 during steady-state experiments. In vitro experiments indicated that diethylstilbestrol monoglucuronide forms an association with taurocholate, as well as the micellar structures of bile, resulting in a severalfold enhancement of solubility above that in aqueous buffer alone. Taurodehydrocholate, a non-micelle-forming bile salt, did not interact with this metabolite and had no effect on its solubility. Substitution of taurodehydrocholate for taurocholate during the steady-state infusion of diethylstilbestrol produced no significant changes in the transport of diethylstilbestrol monoglucuronide from blood to bile.