The objective of this work is to study the dietary regulation of cytosolic NADP-linked isocitrate dehydrogenase (EC 1.1.1.4.2) in male rat liver. Seven different diets were prepared: 1- AIN-93 (control), 3501 kcal/g diet; 2- Soy, 3540 kcal/g diet; 3- Low protein, 3593 kcal/g diet; 4- Dextrin, 4056 kcal/g diet; 5- High- carbohydrate, 4101 kcal/g diet; 6- Fat, 4120 kcal/g diet and 7-High- fat, 6521 kcal/g diet. The enzymatic activities of isocitrate dehydrogenase and glucose-6-phosphate dehydrogenase, as marker enzyme, were determined. The variation of some serum parameters as glucose, total cholesterol and triglycerides, was studied. The results showed that isocitrate dehydrogenase did not change significantly with different diets, while for glucose-6-phosphate dehydrogenase, significant differences were observed for each diet respect to control. Glucose, cholesterol and triglycerides did not show any difference to diets 2 and 3, compared with diet 1. In hypercaloric diets, there was a significative increase (p< 0.001) in glucose and triglycerides, while with cholesterol a significative decrease was observed. Likewise, the response of isocitrate dehydrogenase to starvation during 48 hours and refeeding fat diet, was studied and the enzyme activity did not show any modification in relation to the control. We could conclude that isocitrate dehydrogenase should not be under nutritional regulation, whereas glucose-6-phosphate dehydrogenase, glucose, cholesterol and triglycerides, are regulated by the diet. (C) 1999 Elsevier Science Inc.