Human immunodeficiency virus infection is characterized by a progressive depletion of helper T-lymphocytes and, like allergic diseases, is associated with altered T cell regulation. Total serum IgE was measured in 67 infected male subjects, 27 uninfected heterosexual male subjects, and 18 uninfected homosexual male subjects. The mean IgE level (132 IU/ml) of infected subjects with a helper T-lymphocyte number less than or equal to 200/mm3 was significantly greater than mean IgE levels of the uninfected heterosexual (38 IU/ml) and homosexual (35 IU/ml) groups. IgE levels were inversely related to both helper T cell and suppressor/cytotoxic T cell numbers but not to IgG or IgA levels. The increase in IgE was not a reflection of an increased prevalence of atopic disease (allergic asthma, allergic rhinitis, or atopic dermatitis) in the infected subjects. The elevation of IgE may be related to a difference among the groups in T cell production of IgE regulatory lymphokines.