Short-term effects of estradiol on gluconeogenesis, redox state and on the activities of the enzymes involved in NADPH production have been examined. Hepatocytes incubated with estradiol (10(-4)M) showed a decreased gluconeogenesis and an increased lactate/pyruvate ratio. The malic enzyme was found to be stimulated by 45%, whereas glucose-6-phosphate dehydrogenase and isocitrate dehydrogenase activities were not affected by the presence of the hormone. Estradiol produced selective inhibitions of glucose synthesis from various substrates and diminished malate dehydrogenase activity by 22%. The possibility that the estradiol-induced alterations here reported are related to the hormone catabolism itself in the liver is suggested. Other results in this work call attention to the importance of the vehicle used for the steroid dispersion. Propylene glycol markedly alters the metabolic state of liver cells and also antagonizes the modifications produced by estradiol.