Recent in vitro investigations have demonstrated that corticosteroids in combination with interleukin-4 induce the synthesis of IgE. Corticosteroids are increasingly being used to treat the inflammatory component of asthma. This has raised concern over the potential in vivo effects of corticosteroids on IgE production and the correlation of IgE-enhancing effects with clinical effects on asthma. In this study 10 patients with asthma were given a 7-day course of 20 mg of prednisone, administered orally two times a day. All of the patients had a rise in serum IgE levels after the course of prednisone (p = 0.005). Detection of specific IgE to pollen and perennial allergens demonstrated that the rise in serum IgE was polyclonal. Peripheral blood mononuclear cells from patients treated with prednisone produced increased levels of IgE in vitro when exogenous IL-4 was added to their cultures. Peripheral blood mononuclear cells obtained from patients before and after administration of prednisone revealed a significant decrease in interferon-gamma synthesis (p = 0.005), but not in interleukin-4 (p = 0.6), after the course of prednisone. These findings were paralleled by a significant decrease in the frequency of interferon-gamma (p = 0.03), but not interleukin-4 (p = 1.0) expressing cells. Despite the increase in IgE synthesis, there was a significant increase in forced expiratory volume in 1 second after the course of prednisone (p = 0.01). These data suggest that the observed rise in IgE production associated with prednisone treatment is not clinically deleterious but reflects the immunomodulatory effects of corticosteroids on T lymphocytes.