Immunocytochemistry was used to demonstrate tyrosine hydroxylase (TH)-positive profiles in the spleen of the adult Fischer 344 rat. At the light microscopic level, numerous varicose nerve profiles were seen in the white pulp, particularly surrounding the central arteries and their arteriole branches. At the electron microscopic level, varicosities were seen in close proximity to smooth muscle cells of the arteries, and directly abutting lymphocytes (presumable T-lymphocytes) of the nearby periarteriolar lymphatic sheath. There were no intervening cell processes between the TH-positive terminals and the lymphocyte. The opposing membranes were smooth and evenly spaced approximately 6 nm apart. Additional TH-positive nerve profiles were seen in the inner marginal zone and within trabeculae. The correlation between this immunocytochemical staining and previously demonstrated histofluorescence for norepinephrine leads to the conclusion that lymphocytes in the splenic white pulp have direct associations with noradrenergic fibers of the sympathetic nervous system. This association provides a route by which the autonomic nervous system could directly influence specific immune system effector cells.