Peripheral hyperinsulinaemia is the cause of metabolic changes that might contribute to the high incidence of macrovascular disease in patients with diabetes mellitus. In order to test this hypothesis muscle biopsies from 12 Type 2 diabetic patients and 14 age and sex matched non-diabetic patients, undergoing minor surgery, were obtained. The diabetic patients had significantly elevated fasting serum insulin (0.29 +/- 0.05 vs 0.06 +/- 0.03 nmol-1) and glucose (8.3 +/- 1.5 vs 4.6 +/- 0.5 mmol-1) and HbA1 levels (8.4 +/- 0.4 vs 5.0 +/- 0.2 per cent). The fasting and 2-h postprandial C-peptide levels were 0.99 +/- 0.25 vs 0.39 +/- 0.12 and 3.12 +/- 0.75 vs 1.09 +/- 0.34 nmol/l, respectively. The diabetic patients showed a marked elevation of triglyceride in the striated muscle biopsies compared to the non-diabetic controls (290 +/- 52 vs 48 +/- 6 mumol/g wet weight, p less than 0.001). Moreover, the activities of glucose-6-phosphate dehydrogenase (0.25 +/- 0.03 vs 0.13 +/- 0.01 U/g wet weight) and malic enzyme (0.15 +/- 0.01 vs 0.05 +/- 0.01 U/g wet weight), necessary for lipid synthesis, were significantly increased (both p less than 0.001) in the diabetic patients while the glycolytic enzymes, hexokinase (0.65 +/- 0.09 vs 1.82 +/- 0.11 U/g wet weight), pyruvate kinase (7.3 +/- 0.9 vs 13.2 +/- 0.9 U/g wet weight), phosphofructokinase (1.3 +/- 0.2 vs 2.6 +/- 0.2 U/g wet weight), and alpha-glycerophosphate dehydrogenase (7.3 +/- 0.5 vs 12.5 +/- 0.7 U/g wet weight) were decreased (all p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)