Glucose intolerance is influenced by body fat mass, as well as muscle fiber composition. To examine the relation between the metabolic profile and muscle morphology in this condition, we performed muscle biopsies and hyperglycemic clamps to determine insulin secretion and clearance, and the insulin effects on glucose disposal and nonesterified fatty acids (NEFA) in 45 glucose intolerant persons (body mass index [BMI], 27.8 +/- 3.0 kg/m2) and 45 normoglycemic controls (BMI, 25.8 +/- 2.7 kg/m2) (P = .001). After adjustment for BMI, glucose-intolerant subjects had lower first-phase insulin release (726 v 954 pmol/L, P = .04). Glucose-intolerant subjects and controls differed in fasting insulin, insulin clearance, and insulin sensitivity to glucose disposal before, but not after, standardizing for BMI. During the clamp, glucose-intolerant subjects had less NEFA suppression and elevated levels of NEFA compared with controls (85% +/- 9% v 90% +/- 6%, P = .02; and 70 +/- 42 micromol/L v 45 +/- 28 micromol/L, P = .01). Glucose-intolerant subjects also had a higher percentage of insulin-insensitive, type 2b muscle fibers, which are not adapted for fat oxidation (7% +/- 9% v 9% +/- 9%, P = .003). BMI was not associated with NEFA suppression or the percentage of type 2b muscle fibers in either group. In conclusion, glucose-intolerant persons have impaired first-phase insulin release, an elevated percentage of type 2b muscle fibers, and increased NEFA availability. Reduced insulin clearance, hyperinsulinemia, and insulin resistance were associated with small increments in BMI.