Expression of muscarinic cholinergic receptors (m-AchR) on thymocytes and lymphocytes supports a hypothesis of direct interaction between autonomic innervation and the immune system. Using a muscarinic antagonist, [3H]quinuclidinyl benzilate ([3H]QNB), we revealed different characteristics of m-AchR expression in lymphocytes isolated from the spleen, peripheral blood or thymus of Wistar rats. To further explore the mechanisms controlling m-AchR expression in lymphocytes we have addressed two questions: (i) whether local brain lesions will affect [3H]QNB binding activity of lymphocytes and (ii) whether different antigens will alter m-AchR expression in lymphocytes. We report here that electrolytic lesions of the area hypothalamica anterior resulted in a significant increase in [3H]QNB-specific binding in thymocytes 7 days after neurosurgery. In contrast, local lesions of other hypothalamic structures (area preoptica medialis, area hypothalamica posterior) or sensomotor cortex did not affect m-AchR expression in thymocytes. No apparent changes of [3H]QNB-binding activity were found in lymphocytes isolated from rat spleen or peripheral blood after operation. Both T-cell-dependent (sheep red blood cells) and T-cell-independent (Vi antigen of Salmonella typhi) antigens induced a significant increase in [3H]QNB-specific binding in spleen lymphocytes while [3H]QNB-binding activity of peripheral blood lymphocytes did not change. A different pattern of lymphocyte m-AchR expression found in various lymphoid tissues after immunization or brain lesions suggests a local involvement of cholinergic mechanisms in neuroimmune interaction.