Colchicine is secreted into bile as a major pathway of elimination. Cyclosporine (CsA) inhibits colchicine biliary secretion. In the present study, the effects of cyclosporine and its vehicle (cremophor) on the partitioning of colchicine across the liver were studied. CsA decreased the colchicine bile/plasma ratio from 484±39 to 53±3 (P<0.001). this="" effect="" was="" due="" to="" both="" a="" decrease="" in="" bile/liver="" partitioning="" (control,="" 35.1±1.2,="" vs="" csa="" treatment,="">p<0.001) as="" well="" as="" a="" decrease="" in="" liver/plasma="" partitioning="" (conrol,="" 13.7±0.8,="" vs="" csa="" treatment,="">P<0.001). cremophor="" also="" decreased="" the="" colchicine="" bile/plasma="" ratio="">P<0.02 vs="" control),="" but="" this="" effect="" was="" due="" to="" a="" decrease="" in="" the="" liver/plasma="" ratio="">P<0.02 vs="" control)="" rather="" than="" the="" bile/liver="" ratio="">P>0.2 vs control). Inhibition at the canalicular membrane is consistent with the location of gp-170, the presumed transporter of colchicine.