In the study, the effect that 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has on the antibody plaque-forming cell (PFC) response to sheep red blood cells (SRBC) in adult female B6C3F1 mice and F344 rats was compared. The effect that TCDD has on the PFC response of male F344 and female Long-Evans rats was also determined. Mice or rats were given a single intraperitoneal injection of TCDD at doses ranging from 0.1 to 30 micrograms/kg, 7 days prior to intravenous immunization with SRBC. Four days later the PFC response to SRBC was determined. Results demonstrate species differences in the effect of TCDD on the PFC response to SRBC which were unrelated to hepatic CYP1A1 or CYP1A2 induction, time to peak response, gender, and strain. The failure of TCDD to suppress and in fact to enhance the PFC response to SRBC in rats appears to be related to alterations in splenic CD4(-)CD8(+) lymphocytes.