Long-term (30 wk) effects on serum lipoproteins and insulin sensitivity of two diets, one with a low polyunsaturated to saturated fat ratio (P:S 0.3) and one with a P:S of 1.0, were compared in 14 patients with noninsulin-dependent diabetes mellitus (NIDDM) in a crossover study. Total and LDL-cholesterol levels declined by 7.6% (p less than 0.01) and 9.8% (p less than 0.01), respectively, during the high P:S diet. VLDL-, HDL2-, and HDL3-cholesterol; triacylglycerol; and apolipoprotein A1, A2, and B levels were not affected by the change in P:S. Despite a modest increase of insulin-mediated glucose disposal at physiologic insulinemia during the high P:S diet, no influence was seen on glycemic control, and on blood glucose, plasma insulin, and C peptide responses to mixed meals. In conclusion, a linoleic-enriched diet in patients with NIDD causes a less atherogenic lipoprotein profile but does not influence glycemic control and carbohydrate tolerance.