Elevation of IgE has been associated with T-cell dysregulation and with the occurrence of opportunistic infections in patients with acquired immunodeficiency syndrome. The precise cause of IgE overproduction during the early stages of human immunodeficiency virus (HIV)–1 disease, however, has not been established. In light of reports demonstrating that IgE production may be affected by vitamin E levels in an animal model, we evaluated nutritional status in relationship to plasma IgE levels and immune parameters in 100 asymptomatic HIV-1–seropositive and 42 HIV-1–seronegative homosexual men. Approximately 18% of the HIV-1–seropositive population demonstrated biochemical evidence of plasma vitamin E deficiency (<5 μg/ml). Subsequent analysis of available samples indicated a dramatic elevation of IgE levels (308 ± 112 IU/ml) in vitamin E–deficient seropositive subjects ( n = 9) as compared with age and CD4-matched HIV-1–seropositive persons with adequate vitamin E levels (n = 16, 118.1 ± 41.1 IU/ml) and significantly lower levels (59.5 ± 15.7 IU/ml) in HIV-1–seronegative men (n = 20, p = 0.01). This effect, which was independent of CD4 cell count, did not appear to be influenced by atopic or gastrointestinal parasitic disease. The low plasma vitamin E levels were related at least in part to dietary intake (r = 0.552, p = 0.01), suggesting that supplementation may be warranted in HIV-1–infected persons in whom vitamin E deficiency develops. Analysis of covariance revealed a strong relationship between IgE levels and CD8 cell counts (p < 0.006), and between IgE level and vitamin E deficiency (p < 0.039). Although nutritional deficiency is unlikely to be the principal cause of immunoglobulin dysregulation in HIV infection, these results demonstrate that vitamin E deficiency may play a contributory role in IgE elevation during the early stages of disease. (J ALLERGY CLIN IMMUNOL 1995;95:886-92.)