Effects of fenfluramine on hepatic intermediary metabolism have been studied using the isolated hepatocyte system. Fenfluramine inhibits the formation of glucose from lactate plus pyruvate and from alanine as well as the production of ketone bodies from added oleate. The latter observation suggests that inhibition of gluconeogenesis may result from a decrease in the level of mitochondrial acetyl-CoA. Fatty acid synthesis by hepatocytes is slightly stimulated by fenfluramine, perhaps as a consequence of the increase in cytosolic reducing equivalents, observed as an increase in the ratio of lactate/pyruvate.