Cytochrome P450IIE1, a member of the cytochrome P450 supergene family, was measured in peripheral lymphocytes of 14 patients with insulin-dependent diabetes mellitus who were in poor metabolic control, as evidenced by elevated hemoglobin A1 levels (mean, 11.9 +/- 2.8%; normal, less than 7.8). Only one major form (mol wt, 48,000 daltons) of cytochrome P450IIE1 was detected with a specific polyclonal antibody against P450IIE1. Levels of cytochrome P450IIE1 were very low to undetectable in human lymphocytes from seven normal subjects. However, levels of P450IIE1 were elevated in lymphocytes from patients with insulin-dependent diabetes mellitus. Elevated levels of cytochrome P450IIE1 determined by immunoblot analysis correlate positively with the levels of hemoglobin A1 (r = 0.8), a metabolic indicator in diabetic subjects. In one study subject in whom diabetic control was improved, the drop in hemoglobin A1C levels was accompanied by normalization of P450IIE1 levels.