We evaluated the hypothesis that plasma cholesteryl ester transfer (CET) and lipase activities are influenced by insulin sensitivity and contribute to the low high-density lipoprotein (HDL) cholesterol observed in type 2 diabetic patients and insulin-resistant non-diabetic subjects. Sixteen type 2 diabetic and 16 non-diabetic subjects participated. Diabetic and non-diabetic subjects were divided in equal groups of eight subjects with low or high insulin sensitivity, which was documented as the glucose infusion rate (M-value) during the last hour of a 3-h euglycaemic hyperinsulinaemic clamp (150 mU kg(-1) h(-1), blood glucose target 4.6 mmol L(-1)). Post-heparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities were measured in samples obtained 1-2 weeks before the clamp. Plasma CET was measured by a radioisotope method. Compared to non-diabetic men with high insulin sensitivity (n = 8) HDL cholesterol was lower in type 2 diabetic men (n=8, p<0.01) and non-diabetic men (n=8, p <0.05) with low insulin sensitivity, and the HDL cholesterylester content was lower in type 2 diabetic men with high insulin sensitivity (n=8, p<0.05). In non-diabetic subjects with high insulin sensitivity, plasma CET was lower than in the other groups (p<0.05 for all). Multiple regression analysis showed that plasma CET (p=0.001) and HL activity (p=0.02) were independently and negatively associated with the M-value. No association between the M-value and LPL activity was observed. Independent negative relationships of HDL cholesterol with plasma CET (p = 0.04) and HL activity (p=0.03) were observed. This study supports the hypothesis that a low HDL cholesterol associated with insulin resistance in type 2 diabetic and non-diabetic subjects is related to a high plasma CET and a high HL activity.