OBJECTIVE: To determine whether the features of syndrome X are more common in first-degree relatives of non-insulin-dependent diabetes mellitus (NIDDM) patients than in control subjects with no family history of diabetes. RESEARCH DESIGN AND METHODS: A total of 154 first-degree relatives from 60 families with two or more NIDDM patients and 154 age- and sex-matched control subjects were studied. All subjects underwent a 75-g oral glucose tolerance test and baseline lipid blood and anthropometric measures. The features of syndrome X that were studied were obesity, hypertension, dyslipidemia (high triglyceride levels and low high-density lipoprotein [HDL] cholesterol concentrations), impaired glucose tolerance (World Health Organization criteria), and insulin resistance (as assessed by the homeostasis model assessment). RESULTS: Relatives were heavier than control subjects (body mass index 27.5 +/- 5.2 vs. 25.2 +/- 4.6 kg/m2, respectively [mean +/- SD], P < 0.0002), had lower HDL cholesterol concentrations (1.2 +/- 0.3 vs. 1.4 +/- 0.4 mmol/l, P < 0.001), were more insulin-resistant (2.3 [0.7-7.6] vs. 1.6 [0.5-5.1], geometric mean [95% confidence intervals], P < 0.0001), and had more individuals classified as having impaired glucose tolerance (28 of 154 [18%] vs. 7 of 154 [7%], chi 2, P < 0.001). The differences in insulin resistance and HDL cholesterol concentrations between the groups were independent of obesity. CONCLUSIONS: Features of syndrome X occur more frequently in relatives of NIDDM patients than in control subjects with no family history of diabetes.