Insulin resistance is a common feature in first-degree relatives of NIDDM patients. To explore the mechanism(s) behind this condition in more detail, a percutaneous muscle biopsy (vastus lateralis) was performed in 25 first-degree relatives of NIDDM patients and 21 control subjects to examine muscle fiber composition and capillary density. Insulin-stimulated glucose disposal (R_d) was determined employing a hyperinsulinemic-(insulin infusion rate 0.6 mU · kg⁻¹ · min⁻¹) euglycemic clamp. R_d (5.76 ± 0.35 vs. 8.06 ± 0.36 mg · kg lean body weight [LBW]⁻¹ · min⁻¹ P < 0.001) and estimated Vo_2max (49.3 ± 2.8 vs. 57.2 ± 3.5 mg · kg LBW⁻¹ · min⁻¹, 0.05 < P < 0.10) were decreased in the relatives. The number of type lib fibers (29.5 ± 2.5 vs. 21.0 ± 2.8%, P < 0.05) was increased in the relatives, whereas no significant differences were found in other fiber types or capillary density between the groups. Correlations were observed between number of type I fibers (positive), number of type lib fibers (negative), and capillary density (positive) versus R_d as well as estimated Vo_3max (P < 0.05). In a multiple linear regression analysis with R_d as a dependent variable, estimated Vo_2max, family history of NIDDM, and number of type lib fibers (P < 0.001, r² = 0.64) significantly determined the level of R_d, whereas capillary density did not. In conclusion, insulin-resistant first-degree relatives of NIDDM patients are characterized by an increased number of type lib muscle fibers. Whether this finding reflects a reduced physical activity level and fitness in the relatives or is of primary genetic origin remains to be determined.