To investigate the effects of carnitine on insulin sensitivity in non-insulin-dependent diabetes, insulin-mediated glucose disposal was measured in nine diabetic patients (age 54 +/- 3 years, BMI 27 +/- 1 kg/mq) during a primed (3 mmol) constant (1.7 mumol/min) intravenous infusion of carnitine. In control experiments, the same patients received saline instead of carnitine. Plasma glucose concentration was maintained constant at the level of 100 mg/dl during both studies while plasma insulin was raised to a plateau of 60 microU/ml. Despite similar insulin levels, whole-body glucose utilization was higher with carnitine (4.05 +/- 0.37 mg/kg/min) than saline infusion (3.52 +/- 0.36). Blood lactate concentrations were similar in the basal state and decreased significantly during carnitine infusion (P less than 0.05-0.005), whereas it remained substantially unchanged during saline infusion. Plasma FFA decreased to a similar level (0.1 mmol/l) in both studies. We conclude that an acute carnitine administration is able to improve insulin sensitivity in NIDDM patients. The lactate data suggest that this effect may at least in part be mediated by carnitine activation of pyruvate dehydrogenase.