The effect of phenformin on the induction of plasma triglyceride by high-carbohydrate feeding was studied in ten subjects (nine normals and one Type II, hyperlipoproteinemia). Each study was divided into four periods. During periods I and III, each subject received an American Diabetes Association diet calculated to maintain body weight and in periods II and IV a high-carbohydrate diet (85 per cent of the calories derived from carbohydrate) which was isocaloric with the control diet. Phenformin, 50 mg. twice daily, was administered in either period II or IV in association with the high-carbohydrate diet. There-was no change in weight during the study. The plasma triglyceride increase (ATG) during the high-carbohydrate diet alone was 103 mg. per cent as compared with a ATG of 26 mg. per cent during the high carbohydrate-phenformin period, a highly significant difference (p < 0.005).Insulin secretion and glucose tolerance during each period was determined by the sum of the increments above baseline of plasma insulin and glucose concentrations during a five-hour oral glucose tolerance test. No significant differences in glucose tolerance or in insulin secretion occurred during any of the periods despite the alterations produced by the high-carbohydrate diet and phenformin in plasma triglyceride concentrations. A slight correlation could be demonstrated between the insulin response to a glucose load while on the control diet and the magnitude of the triglyceride response on the high-carbohydrate diet. Tlie data indicate that (1) phenformjn inhibits the induction o£ plasma triglyceridg_4uu>ducod by carbohydrate loading, (2) there was no correla^^n^^_w^en_.the._£hflji£e.s.in_ plasma..triglyceride concentrations, glucose tolerance or insulin responsiveness during thie experimental periods and (3) the magnitude of the-increase in plasma triglyceride concentration may be related-to the insulin response to a glucose load during the control period. DIABETES 20:739-44, November, 1971. Although carbohydrate-induced hypertriglyceridemia is frequently associated with adult-onset diabetes mellitus and/or obesity, 1 its relationship to the utilization of carbohydrate and to insulin secretion is unclear. Since hyperinsulinemia is common to both adult-onset diabetes and obesity, 2 -3 the induction and/or maintenance of hypertriglyceridemia by carbohydrate has been attributed to increased insulin secretion. 4 " 6 The results of studies, however, which relate triglyceride induction to changes in insulin secretion have been conflicting and for the most part have been confined to patients with lipoprotein abnormalities. 4 " 7 Since the induction of plasma triglyceride levels by carbohydrate is not limited to patients with lipoprotein abnormalities, we thought that