The influence of obesity on blood pressure and plasma lipoproteins, glucose and insulin levels was investigated in patients with familial combined hyperlipidaemia (FCH). Sixty seven FCH patients mean age 49.0 +/- 8.9 y (45 male, 22 female) defined as obese (BMI > or = 27 kg/m2, n = 39) or non-obese (BMI < 27 kg/m2, n = 28) were compared with control subjects matched for age, gender and body weight. Blood pressure, plasma lipoproteins, glucose and insulin were measured at baseline and following standard oral glucose load. The analysis indicate that FCH subjects with BMI > or = 27 kg/m2 had significantly higher systolic and diastolic blood pressure, blood glucose and insulin levels following oral glucose tolerance test than those with BMI < 27 kg/m2. Fasting plasma insulin values were also significantly higher in the BMI > or = 27kg/m2 subjects (138.5 +/- 66.6 vs 111.0 +/- 29.9 pmol/l, respectively, P < 0.05). Quantification of the area under the curve of the insulin secretion showed hyperinsulinaemia in 64.1% of patients with BMI > or = 27kg/m2 compared to 28.5% in the group with BMI < 27 kg/m2 (P < 0.01). Plasma insulin values were positively related to triglyceridaemia. There were no differences in the plasma lipid values between the two FCH groups. We conclude that fasting and post-glucose stimulated plasma insulin levels are frequent findings in patients with FCH when compared with control subjects of similar age, gender and BMI. Moreover, obesity (BMI > or = 27kg/m2) exacerbates the hyperglycaemia, hyperinsulinaemia and blood pressure values in these FCH subjects. These factors, together with lipid abnormalities, can predispose to the elevated risk of cardiovascular disease observed in FCH subjects.