In 10 hypercholesterolemic patients with Type I (insulin-dependent) diabetes, simvastatin 10-40 mg/day was compared to placebo in a randomized, double-blind, cross-over study with treatment periods of 12 weeks. Between each treatment there was a wash-out period of 4 weeks. Compared to placebo, simvastatin reduced total cholesterol by 19% (p less than 0.001) and low density lipoprotein (LDL) cholesterol by 24% (p less than 0.001). Simvastatin therapy reduced plasma triglyceride by 8% and increased high density lipoprotein (HDL) cholesterol by 8%, but neither of these alterations was significant (p greater than 0.05). Diabetic control and daily requirement of insulin were not influenced by simvastatin. In six patients, all men, there were no alterations in the concentrations of dehydroepiandrosterone-sulphate, testosterone, estradiol, prolactin, luteinizing hormone or follicle-stimulating hormone, while sex hormone-binding globulin was significantly (19% (p less than 0.05)) reduced during therapy with simvastatin. Thus, in Type I (insulin-dependent) diabetic patients, simvastatin causes significant reductions in plasma total cholesterol and LDL cholesterol which are similar in magnitude to those observed in non-diabetics. This favourable effect can be obtained without any concomitant negative influence on glucose regulation or total gonadal steroid hormone concentrations.