Plasma glucose, insulin levels and hepatic glucose production rates were studied after an overnight fast in six Addisonian patients in three different conditions: off replacement treatment, on substitution therapy and on high-dose glucocorticoid treatment. For comparison eight normal subjects were evaluated in basal conditions. Fasting plasma glucose and hepatic glucose production did not change significantly with either level of glucocorticoid treatment when compared to the untreated state and the normal controls, but there was a significant increase in plasma glucose levels in the high-dose cortisone-treated Addisonian patients when compared to the untreated state. Insulin levels were significantly lower in the untreated state and significantly higher in the high dose-treated patients when compared to the normal controls. It is suggested that in these experimental conditions the peripheral actions of glucocorticoids are predominant over the hepatic effects by virtue of their ability to produce secondary changes in insulin levels, keeping the hepatic glucose production constant.