Immunoautoradiographic techniques were used to determine the topographical distribution of interleukin 2-like immunoreactivity and interleukin 2 receptor-like immunoreactivity (Tac antigen-like immunoreactivity) in rat brain. Interleukin 2 receptors were also visualized by film autoradiography using I-125-recombinant human interleukin 2. Endogenous interleukin 2-like immunoreactive material was present in a limited number of brain regions. The highest densities were localized to the median eminence-arcuate nucleus complex, hippocampal formation, lamina IV of the cerebral cortex, lateral septum, neostriatum and cerebellum. Lower levels of interleukin 2-like immunoreactive material were present in the thalamus, medial septum and granule cell layer of the cerebellar cortex. Tac antigen-like immunoreactivity was observed in virtually the same brain regions, and within these brain regions showed the same distribution as interleukin 2-like immunoreactivity. In contrast, [I-125]interleukin 2 binding sites were only detected in the hippocampal formation and the molecular layer of the cerebellar cortex. Quantitative analyses confirmed that there was a positive correlation between the densities of interleukin 2-like immunoreactivity and interleukin 2 receptor immunoreactivity (Tac antigen-like immunoreactivity) in various brain regions, suggesting that interleukin 2 is synthesized and/or stored in the vicinity of the site of interaction with the Tac antigen of its receptor. Overall, the presence of endogenous interleukin 2-like immunoreactive material and interleukin 2 receptor-like immunoreactive material in selective regions of the rat brain suggests that this neurokine may normally act to regulate a variety of brain functions in the adult rat.