Chenodeoxycholic acid (CDCA) is an effective treatment for dissolving gallstones but experimental studies have suggested that it might be hepatotoxic. A group of patients underwent medical therapy for gallstones for periods of 30 days up to 14 mo. with CDCA (15 mg/kg per day). Routine functional tests, determination of some liver microsomal enzymes and stereological studies of the liver tissue were performed and the data compared with those obtained before treatment. No significant changes were observed in the functional tests throughout the study. The microsomal mixed function oxidase system seemed unaffected by CDCA therapy. The histological features of the liver biopsies were not appreciably different from those observed prior to treatment. Although there were large interindividual variations, the volume desnity of parenchymal steatosis and of the lipocytes remained comparable in the same individual. The ultrastructural features noted in untreated subjects such as curled mitochondrial cristae, slight intracellular bile retention, increased surface density of the rough endoplasmic reticulum were still evident after 14 mo. of treatment. No additional changes were noted. No evidence of hepatotoxicity seems to develop in man under therapy with CDCA at the dose considered. But the structural abnormalities observed before treatment appear to persist even in subjects under long-term therapy.