The relationships between plasma malondialdehyde (MDA) and metabolic parameters in type I and II diabetic subjects have been studied at different levels of glycemic control. In 67 diabetics (20 type I, 47 type II, aged 53 +/- 1.2) and 40 healthy subjects (aged 47 +/- 1.75), triglycerides (TG), total cholesterol (CT) and C-HDL, fasting blood glucose (FBG), glycosylated hemoglobin (GHb) and MDA were measured. Diabetic population as a whole showed higher MDA plasma levels compared to controls, together with higher FBG, TG, GHb. MDA showed a significant correlation with both FBG and GHb, but was not correlated to plasma lipids. The patients with a poor metabolic control showed the highest plasma MDA concentrations, significantly different from the group with a better control: GHb less than 10% = MDA 2.77 +/- 0.28 nmol/ml - GHb greater than 10% = MDA 4.22 +/- 0.39 nmol/ml (z = 2.10, a less than 0.02); FBG less than 150 mg/dl = MDA 2.74 +/- 0.32 nmol/ml - FBG greater than 150 mg/dl = MDA 4.15 +/- 0.37 nmol/ml (z = 2.22, a less than 0.02). Glycemic equilibrium seemed to influence plasma MDA, increasing free radical production. This phenomenon probably occurred either because of enhanced glycosylation and platelet aggregation, or impairment of cellular antioxidant protective systems. The increased free radical production may play a role in the pathogenesis of metabolic vasculopathy.