Plasma lipids and oral glucose tolerance were determined in 67 normal control subjects (age range 19-67 yr) and 150 individuals (17-69 yr) who were offspring of two type II diabetic parents. Age- and weight-adjusted analyses of covariance were performed for lipids and for glucose and insulin responses. For both men and women, the mean concentrations of total, low-density-, and high-density-lipoprotein-cholesterol and of triglycerides in the offspring with normal glucose tolerance (N = 109) were similar to respective controls. For offspring with abnormal glucose tolerance (N = 41), the mean levels of total cholesterol, LDL-cholesterol, and triglycerides were significantly elevated (P = 0.02 or less) in women but not in men. The mean HDL-cholesterol levels were 20% lower and LDL/HDL-cholesterol ratios 60% greater in women with abnormal glucose tolerance, whereas no significant differences existed for any of the lipid fractions in men, compared with respective controls. Both men and women with abnormal glucose tolerance had a comparable magnitude of hyperglycemia as well as hyperinsulinemia. These observations indicate that significant alterations in plasma lipids exist in individuals with mild, asymptomatic glucose intolerance and there are important sex differences in lipid metabolism in the early stage of diabetes, despite comparable degrees of glucose intolerance and insulin responses.