Spleens from newborn mice less than 6-7 days of age contain 'naturally occurring' suppressor cell populations that are able to inhibit nonspecifically immune responses of third-party adult spleen cells and alloreactivity in the newborn spleen per se. Isolation of the effectors of this suppressor activity reveals that they are not classical T lymphocytes but, instead, a mixed population of cells of the monocyte series (monoblast/promonocyte/monocyte) plus mast cells. This mixed population apparently can elicit its suppressor activity in part through secretion of soluble, in vitro culture-stable material, which in turn initiates activation of the suppressor cell/limb of the immune response. These activities, nevertheless, modulate most strongly the early activation events of T-cell responses and can result in complete suppression of alloreactive helper and cytotoxic T lymphocyte development. Suppressor activity by mast cells can be demonstrated by degranulation, whereas suppressor activity by monocytes appears inherent in the newborn population. Thus, there are now at least three cell populations in the neonate spleen--mast cells, monocytes, and T lymphocytes--which can effect suppressor activity.