By using the euglycemic clamp technique and indirect calorimetry, we determined the degree of insulin resistance in 12 obese (body mass index >27.0 kg/m2), normotensive patients with type IIB hyperlipidemia (HLJIB) (total cholesterol &6.5 mmol/L and total triglycerides S2.0 mmol/L) and 17 control subjects (total cholesterol S6.1 mmol/L and total triglycerides <1.8 mmol/L) who were carefully matched for sex, age, and obesity. Fasting plasma insulin was higher in HLJIB patients than in control subjects (18.4±4.6 versus 8.9±1.2 mU/L, respectively; P=.O1O). The rates of whole-body glucose uptake were significantly lower in HLJIB patients than in control subjects during the last hour of the clamp (42.2 ±3.9 versus 54.6±2.8 /imol/kg per minute, respectively; P=.O13). Glucose oxidation during the last 30 minutes of the euglycemic clamp was lower in HLJIB patients than in control subjects (14.6±0.9 versus 19.0±13 fimo//kg per minute, respectively, />=.O17). Nonoxidative glucose disposal during the last 30 minutes of the euglycemic clamp was also lower in HLIIB patients than in control subjects, but the difference was not statistically significant (27.6±3_3 versus 35.8±2.8 /unol/kg per minute, respectively, P= M 9). Lipid oxidation during the clamp was completely suppressed in control subjects (-0.24±0.44 /tmol/kg per minute) but was significantly less suppressed in the HLIIB patients (0.94±0.29 jumol/kg per minute, P=.O24). Our study shows for the first time that obese patients with type IIB hyperlipidemia are insulin resistant and that this insulin resistance affects both oxidative and nonoxidative glucose metabolism.