The long term effect of clofibrate treatment on the carbohydrate and lipid metabolisms and on insulin secretion was studied in subjects with primary hyperlipoproteinemia and impaired glucose tolerance. Treatment consisted of a diet and 2.0 g clofibrate per day. The body weight, triglyceride and cholesterol levels, glucose tolerance and insulin secretion of 14 patients were monitored for five years. During the first year of treatment the mean triglyceride and cholesterol levels decreased by 80% and 40% respectively. The cholesterol level became fully normal in the course of further treatment, but the triglyceride level did not. The mean reduction of body weight over the five-year period amounted to 5.0 kg. Improvement in glucose tolerance was shown by a significant increase in Conard's glucose assimilation coefficient. Glucose tolerance became completely normal in some cases. In one case diabetes mellitus became manifest. Improvement of the glucose tolerance was accompanied by reduction of glucose-stimulated insulin secretion by about 50% of the original value. The results permit the conclusion that the use of clofibrate for the long-term treatment of hyperlipoproteinemia is still justified. If hyperlipoproteinemia is accompanied by impaired glucose tolerance, clofibrate can also be regarded as having a certain antidiabetic effect during the normalisation of the "metabolic syndrome".