Administration of Interferon-gamma (IFN gamma) is used in the therapeutic approach for mainly cancer treatment and viral infections in vivo. Recently we observed some important pathologic dysfunctions caused by IFN-gamma administration to pregnant mice. This treatment affected not only the growth and development of the feto-placental unit, but also, among other hematologic disorders, caused splenomegaly to the mother. In an effort to explain the observed hypersplenism, we have analysed the behaviour of macrophages, B and T lymphocytes in the spleen of virgin and pregnant mice after intraperitoneal administration of low IFN-gamma doses. Although the percentage of myeloid Mac-1 and F4/80 positive cells in spleen cell suspensions of virgin and pregnant mice do not change with the IFN-gamma treatment, immunoperoxidase staining of frozen spleen sections shows that in pregnant mice the monocytic cells accumulate at the central white pulp area of the organ, whereas in non-pregnant mice these cells are mainly found at the peripheral red pulp area. In contrast, the same treatment was shown to increase the numbers of Ly5 positive B cells in both virgin and pregnant mice, whereas B cells were found to form clusters only in the case of pregnant animals. We also show that IFN-gamma increases the numbers of Tcyt/sup (Ly2 positive cells) and TH (L3T4 positive cells) in the spleen of virgin mice but not in pregnant mice. Both populations display a physiologic distribution in the white pulp of the organ as assessed by immunoperoxidase staining of frozen spleen sections. Interestingly, the distribution pattern of IL-2- and IL-4-producing cells, which reflects the presence of Th1 and Th2 subpopulations was different in pregnant and virgin mice. Gestating females had IL-2 producing cells dispersed in the white pulp area, whereas IL-4 producing cells formed clusters mainly at the periphery of the organ. Virgin females had almost undetectable levels of IL-4 producing cells, whereas IL-2 producing cells were found at the periphery. Our results indicate that IFN-gamma alters the equilibrium between Th1 and Th2 cells, which in turn is responsible for the redistribution of myeloid and lymphoid cells in the spleen of pregnant mice thereby explaining the development of an active immune/inflammatory reaction.