KAY, G., N. TARCIC, T. POLTYREV AND M. WEINSTOCK. Prenatal stress depresses immune function in rats. PHYSIOL BEHAV 63(3) 397–402, 1998.—The aim of the present study was to determine the effect of prenatal stress on immune function in rats. Pregnant rats were stressed by noise and light, three times weekly throughout pregnancy. Experiments were performed on male and female offspring aged 2 months. Cellular immune responses of splenic lymphocytes to B-cell (pokeweed mitogen (PWM) and T-cell (phytohemagglutinin (PHA)) mitogens were measured by [³H]thymidine uptake, and natural killer (NK) cell cytotoxicity in blood and splenic lymphocytes was measured against the murine T-cell lymphoma, YAC-1, by a 4-h [⁵¹Cr] release assay. Prenatal stress suppressed immune function as shown by a) decreased NK cytotoxicity in splenic and blood lymphocytes, indicating that the effect was not confined to a particular immune compartment, and b) decreased rate of proliferation of splenic lymphocytes to PWM and a smaller depressant effect on their response to PHA. The suppression of B-cell proliferation was more marked in the female and that of NK cell cytoxicity, in the male. Prenatal stress did not alter the distribution of subsets of lymphocytes, in either the spleen or blood, indicating that the reduction in proliferative and cytotoxic activity resulted from functional modifications of effector mechanisms in the cells rather from alterations in their migration between immune compartments. The mechanisms underlying this effect of prenatal stress are not clear but could result from an action of maternal stress hormones on the developing fetal neuroendocrine system.