Serum coenzyme Q(10) (CoQ(10): 2-(3.7,11,15,19,23,27,31,35,39-decamethyl-2,6,10,14,18,22,26, 30,34,38-tetracontadecaenyl)-5,6-dimethoxy-3-methyl-1,4-benzoquinone. CAS 303-98-0) and cholesterol levels were measured to assess the effect of cholesterol-lowering therapy in patients with non-insulin-dependent diabetes mellitus (NIDDM). Twenty healthy volunteers, 97 NIDDM patients and 2 patients with familial hypercholesterolemia were studied. None had overt heart failure or any other heart disease, Mean serum CoQ(10) concentrations were significantly (p < 0.01) lower in diabetic patients with normal serum cholesterol concentrations either with or without administration of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (HMG-CoA RIs) including simvastatin (normal: 0.91 +/- 0.26 (mean +/- SD) mu mol l(-1): diabetic with HMG-CoA RI: 0.63 +/- 0.19; diabetic without HMG-coA RI: 0.66 +/- 0.21). CoQ(10) concentrations were higher (1.37 +/- 0.48, p < 0.001) in diabetic patients with hypercholesterolemia. Simvastatin or low density lipoprotein apheresis decreased serum CoQ(10) concentrations along with decreasing serum cholesterol. Oral CoQ(10) supplementation in diabetic patients receiving HMG-CoA RI significantly (p < 0.001) increased serum CoQ(10) from 0.51 +/- 0.24 to 1.47 +/- 0.34 mu mol l(-1) without affecting cholesterol levels. It significantly (p < 0.03) decreased cardiothoracic ratios from 51.4 +/- 5.1 to 49.2 +/- 4.7 %. In conclusion, serum CoQ(10) levels in NIDDRI patients are decreased and may be associated with subclinical diabetic cardiomyopathy reversible by CoQ(10) supplementation.