Porphyria cutanea tarda (PCT) has a known increased incidence of diabetes mellitus and hepatic involvement. We investigated glucose tolerance and glucoregulatory hormone alterations in seven patients with PCT and correlated these results with hepatic histology by percutaneous liver biopsy. Abnormal glucose tolerance was observed in six of the seven patients (87%). Fasting serum insulin levels were normal range, and normal glucose and growth hormone responses to standard, exogenous intravenous insulin were observed. Fasting serum glucagon and urine free cortisol levels were normal in those patients in whom they were measured. While varying degrees of abnormalities were found on histopathologic exam of the liver biopsies, no patient met the criteria for cirrhosis, and none of the patients demonstrated abnormal levels of insulin counterregulatory hormones commonly seen in cirrhosis. Thus, liver disease may not be the sole cause of the observed glucose intolerance and hyperinsulinemia in PCT patients.