Ablation of the peripheral sympathetic nervous system by treatment of adult (axotomy) and neonatal (sympathectomy) mice with 6-hydroxydopamine hydrobromide produced significant changes in the distribution of cell surface molecules detected on spleen lymphocyte populations. The surface molecules that were studied consisted of the beta-adrenergic receptor and the Thy-1.2 and Lyt-2 surface antigens associated with lymphocyte subpopulations. beta-Adrenergic receptor density, as measured by 3H-dihydroalprenolol binding, was found to be significantly higher on control mouse splenic B cells than on T cells. beta-Adrenergic receptor density was seen to increase in both T and B spleen cell populations after axotomy. The Thy-1.2 and Lyt-2 surface antigens present on cell populations from mouse spleens were labeled using fluorescent monoclonal antibodies and quantitated using a fluorescence-activated cell sorter. A significant increase in the percentage of Thy-1.2 positive cells represented among the total spleen lymphocyte population was detected in axotomized mice. A corresponding increase in the representation of Lyt-2-positive cells, a subset of the Thy-1.2-positive population, was also found. In contrast, while the percentage of Thy-1.2-positive cells per total spleen lymphocyte population were not found to differ between control and sympathectomized mice, a significantly lower percentage of Lyt-2 positive cells within the Thy-1.2-positive population appeared in sympathectomized mice. Suppressor/cytotoxic cell function, as well as properties relating to the recognition of major histocompatibility complex antigens, have been associated with the Lyt-2 antigen. The relative distributions of lymphocyte subpopulations, as indicated by surface markers, and their beta-adrenergic receptors may play an important role in the physiologic functions and interactions between lymphocytes that respond to sympathetic nervous system innervation.