Recently, we observed that impairments exist in skeletal muscle free fatty acid (FFA) utilization during exercise in obese subjects with Type II diabetes. The main objective of the present study was to investigate whether plasma FFA oxidation is impaired during exercise in non-obese Type II diabetic patients. Stable isotope tracers of palmitate and glucose were infused for 2 h at rest and 1h of bicycle exercise at 40% peak oxygen consumption ( V*O(2)max) in volunteers with Type II diabetes and a healthy control group. At rest, plasma FFA oxidation was not significantly different between subjects with Type II diabetes and control subjects (2.13+/-0.51 versus 1.93+/-0.54 micromol.kg(-1).min(-1) respectively). During exercise, Type II diabetic patients and control subjects had similar rates of total fat [Type II diabetes, 9.62+/-1.84 micromol.kg(-1).min(-1); control, 12.08+/-4.59 micromol.kg(-1).min(-1); not significant (NS)] and glucose oxidation (Type II diabetes, 44.24+/-10.36 micromol.kg(-1).min(-1); control, 57.37+/-14.54 micromol.kg(-1).min(-1); NS). No aberrations were present in plasma FFA uptake [rate of disappearance ( Rd ); Type II diabetes, 11.78+/-4.82; control, 10.84+/-3.39; NS] and oxidation rates (Type II diabetes 8.10+/-1.44; control 8.00+/-3.12, NS) in Type II diabetic patients; triacylglycerol-derived fatty acid oxidation was 2.6-fold lower in Type II diabetic patients than in control subjects, but this difference was not statistically significant. Muscle glycogen oxidation was lower in diabetes patients than in control subjects (Type II diabetes, 25.16+/-13.82 micromol.kg(-1).min(-1); control, 42.04+/-10.58 micromol.kg(-1).min(-1); P <0.05) and plasma glucose contributed more to energy expenditure in Type II diabetes (26+/-3% in diabetic versus 15+/-2% in control, P <0.05). We conclude that plasma FFA oxidation is not impaired during exercise in non-obese Type II diabetic patients. The data confirm that Type II diabetes is a heterogeneous disease, and that the adaptation at the substrate level differs between obese and non-obese patients and may contribute to differences in the final appearance of the various phenotypes.