In an attempt to understand the hepatotoxicity associated with immunosuppressive therapy with cy- cloeporin A, we inveatigated the effects of acute cyclosporin A admidstration on biliary secretion, serum bile acid and bilirubin levels and the hietological changes in the hepatic parenchyma in anemthetized male Wjstar rats. The animals were divided into three experimental groups that received equal volumes ( 1 ml, intravenously) of physiological d i n e (controls), cycloqmrin A vehicle (a fat emulsion, Intralipid, mixed with abeolute ethanol) or cycloeporin A dissolved in the aforementioned mixture. In another series of ways, horseradish peroddase was coiqjected with cyclosporin A vehicle or with the solution containing cyclosporin A. Only after cycloeporin A administration was an immediate inhibition in bile flow and in the biliary concentrations and secretion of bile acids and bilirubin found. In addition, a delay in the peak time of the appearance of horseradish peroxideee together with a reduction in the biliary excretion rate and in the total amount of horseradish peroddaae excreted were obeerved during choleataeis. At 40 to 50 min after drug admidstration, all biliary parameters evaluated had returned to the pretest values. The relationship between bile flow and bile acid secretion showed that cycloeporin A-induced cholestasis is related to a decrease of both the bile acid-dependent and bile acidindependent fractions of bile flow. At the end of the cycloeporin A assays, the serum bile acid, total bilirubin and conjugated bilirubin concentrations were greater than those obeerved in the controls and Intralipid-treated animals. These effects were dosedependent. Light microscopy and transmission electron microecopy studies did not reveal architectural hepatic abnormalities. We conclude that cyclosporin A interferes with the hepatocellular vesiclemediated transport processes and poetdate that apart from the previouely proposed inhibition of the hepatic