Mitogen-stimulated lymphocytes recently were shown to release colony-stimulating activity (CSA), a stimulator of granulopoiesis in vitro. Whether CSA release is a result of specific antigen-lymphocyte interactions was investigated by determining the ability of spleen lymphocytes isolated from Trichinella spiralis and BCG infected mice to release CSA. Lymphocytes were incubated with different antigens to obtain conditioned media (CM). Conditioned media prepared from Trichinella-sensitized lymphocytes incubated with Trichinella antigen (CM-1) resulted in a 4-fold increase in the number of colonies from murine marrow cultured in methylcellulose as compared to controls. The addition of Trichinella antigen to nonsensitized or BCG-sensitized lymphocytes did not stimulate CSA release. Similar results were obtained with lymphocytes from BCG-infected mice. Liquid cultures stimulated with CM resulted in an increase in 3H-thymidine incorporation and cell numbers. Using CM-1 to stimulate marrow from Trichinella-infected mice resulted in a 3 to 4-fold increase in the number of eosinophils present after 4 days. All other CMs tested stimulated only neutrophil production. The neutrophilic and eosinophilic responses seen in some immunologic reactions may depend on the release of soluble products from lymphocytes sensitive to the challenging antigen.