The interacting effects of diet and glucocorticoid (GC) on the tritium incorporation into lipid and glucose-6-phosphate dehydrogenase activity in starved-refed rats was studied. Male Sprague-Dawley rats were intact, adrenalectomized (ADX), or ADX and given GC and fed either ad libitum or not fed for 48 hours amd refed either a 65% glucose diet, 65% sucrose diet, 65% starch diet, 65% protein diet or a 40% fat diet. No diet differences in rates of 3HOH incorporation into total lipids were observed in ad libitum-fed rats. ADX lowered lipogenesis and this effect was diet dependent. Sucrose-fed, glucose-fed and protein-fed ADX rats had lower rates of lipogenesis than their intact controls. Starvation-refeeding increased lipogenesis in all groups of intact rats except those fed the 40% fat diet. The magnitude of the response was diet dependent. Sucrose-fed rats had greater responses than fat-fed rats. The diet effect was dependent on the presence of the adrenals and GC. Thus, the large increase in liver lipid associated with starvation-refeeding is contingent on the composition of the diet and the presence of the adrenals.