Numbers of IgM plaque-forming cells (PFC) were reduced by 65% in C57Bl/6 mice given parathion 2 days after immunization with sheep red blood cells (SRBC). The immunosuppressive dose (16 mg/kg, p.o.) caused signs of cholinergic poisoning and 20% mortality. Survivors appeared to have recovered fully from the cholinergic crisis at the time of immunologic assay. However, these animals had reduced tissue cholinesterase (ChE) activities and decreased numbers of nucleated spleen cells. Immunosuppression was apparent on day 4 but not on day 3 or days 5-8 of the primary IgM response. Reduction of serum hemagglutinin titers coincided with reduction of the number of splenic PFC. A lower dose of insecticide (4 mg/kg, p.o.) did not produce signs of poisoning and was not immunosuppressive. The number of 8-day IgG PFC was reduced by 45% when parathion (16 mg/kg, p.o.) was given 6 days after immunization, but not when parathion was given 2 days after immunization. The data suggest that cholinergic stimulation and/or the associated toxic chemical stress may be involved in parathion-induced immunosuppression.