Previous studies have shown that salicylates and protein-calorie malnutrition compromise immunological responses in humans and experimental animals. The present study compared the effects of prenatal normal and low protein diets, with and without aspirin-like drug treatments, on lymphocyte blastogenesis measured by tritiated thymidine uptake for DNA synthesis in splenic lymphocytes from pregnant rats and their offspring following stimulation with the mitogens concanavalin A, phytohemagglutinin, and pokeweed mitogen. Aspirin treatment was associated with increased lymphocyte thymidine uptake for blastogenesis in pregnant rats fed the normal protein control diet and their offspring. The phytohemagglutinin-stimulated increase detected in offspring lymphocytes could not be statistically guaranteed. A low protein diet alone and a normal protein diet combined with salicylamide treatment was associated with decreased blastogenesis in pregnant rats but not in their offspring. Salicylamide or aspirin combined with a low-protein diet decreased blastogenesis in both dams and their offspring. Aspirin combined with a normal protein diet did not adversely affect blastogenesis in either pregnant rats or their offspring. This study suggests that low dietary protein and aspirin-like drugs may independently decrease lymphocyte blastogenesis of pregnant rats and in combination they may also reduce lymphocyte blastogenesis in offspring. The significance of increased lymphocyte blastogenesis in both mothers and offspring following aspirin treatment of pregnant rats fed a normal protein diet is unclear.