There is much discussion about the occurrence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced effects on the human immune system. Extensive studies have been conducted in mice, but those results cannot explain some of the epidemiological data obtained in exposed humans. Therefore, studies in other laboratory animal species are needed. The aim of these experiments was to examine effects of TCDD on cell- and humoral-mediated immunity in male Sprague-Dawley (SD) rats. A delayed-type hypersensitivity (DTH) assay was used to examine cell-mediated immunity. A time-course study demonstrated that TCDD treatment on day -5 relative to immunization (day 0) produced the greatest effect on cell-mediated immunity. In a dose-response experiment, rats were treated with 1, 3, 10, 20, 30, 40 and 90 micrograms TCDD/kg The effect of TCDD on cell-mediated immunity displayed an inverted U-shaped dose-response curve, in that low doses enhanced and high doses suppressed this immune function. This is the first study to demonstrate an U-shaped dose-response curve of TCDD on the immune system. Primary antibody response to sheep red blood cells (SRBC) was used as endpoint to study the effect of TCDD on humoral immunity. Serum anti-SRBC IgM and IgG levels were measured using an enzyme-linked immunosorbent assay (ELISA). In the dose range examined (10, 20 and 40 micrograms TCDD/kg), serum IgM levels were not affected by TCDD compared to controls at 7 and 14 days after immunization. In contrast, serum IgG levels were dose-dependently elevated both 7 and 14 days after immunization, with a maximum increase of 59% over controls.