Involvement of soluble mediator(s) different from interleukin (IL) 1 in the antigen-induced IL 2 receptor expression and proliferation of L3T4' (CD4') T lymphocytes* Proliferation of T lymphocytes (T cells) requires the interaction of interleukin 2 (IL2) with the high affinity form of the IL2 receptor (IL2R). IL2 production as well as IL2R expression are generally induced simultaneously in T cells by the recognition of specific antigen displayed on the surface of syngeneic antigen-presenting cells. The experiments described herein show that the expression of IL 2R has different requirements than the production of IL2 (and other lymphokines). Stimulation of antigenspecific L3T4' T cell lines with antigen-pulsed spleen cells (SC) treated with ultraviolet (UV) light results in efficient IL 2 production but only minimal proliferation due to reduced IL2R expression, as compared to T cells stimulated by antigen and SC without UV light treatment. The reduced IL 2R expression/proliferation correlates with the absence of a soluble mediator(s) termed T cell-stimulating factor (TSF) in the supernatants of T cells stimulated with antigen-pulsed, UV light-irradiated SC. Addition of TSF of these T cells could at least partially restore the proliferative response or enhance IL2R expression. Because TSF is present in the supernatant of T cells triggered by antigen and SC but is absent when the latter are UV light treated, we suggest that TSF is a product of metabolically active splenic antigenpresenting cells. The macrophage products interleukin la + p as well as some other cytokines show no TSF activity.