The food intake, liver composition and hepatic activity of pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G6P-DH), malic enzyme (ME) and acetyl CoA carboxylase (AcCoA Cx) were studied in starved-refed rats. When rats were refed a mixed diet for 3 days, food intake significantly increased (by 33%) from day 1 to 3 and the glycogen accumulation was maximal after 24 hours, but decreased significantly by day 3 (by 34%). In contrast, liver triglycerides sharply increased (10-fold) from day 1 to 3. Furthermore, during refeeding a large increase of G6P-DH, ME and AcCoA Cx was reached on day 3 when the average activity was 5.5- to 6.5-fold higher than before fasting. When rats were refed under conditions of self-selection (carbohydrates, lipids and proteins) total food intake was the same each day, but lipid and carbohydrate intakes varied reciprocally: lipid intake decreased whereas carbohydrate consumption increased during the 3 day refeeding period. Liver glycogen level was unchanged and both the triglyceride accumulation and the overshoot of lipogenic enzymes were highly attenuated: on day 3, they reached 50% of values observed in mixed diet refed rats. Administration of 8-azaguanine during refeeding under self-selecting conditions lowered food intake but had no effect on the pattern of food intake on the first day. In the following days, lipid intake fell dramatically. Azaguanine does not alter liver glycogenesis, but prevents both liver triglyceride accumulation and the overshoot of lipogenic enzymes.