AIM: To explore effects of exogenous and endogenous catecholamines on function of lymphocytes and primary mechanisms mediating the effects. METHODS: Splenocytes of rats were exposed to norepinephrine (NE), α- or β-adrenoceptor antagonists plus NE, or α-methyl-p-tyrosine (α-MT), and then concanavalin A (Con A)-induced intefleukin-2 (IL-2) production and natural killer (NK) cell cytotoxicity were determined by MTT assay and LDH assay, respectively. RESULTS: Optical density (OD) values of NE-treated groups, which reflected IL-2 production,were 0.63, 0.61, and 0.60, respectively for 1×10-10, 1×10-9, and 1×10-8 mol/L NE. They were all significantly reduced in comparison with control value of 0.68 (P＜0.01). The effect of NE was blocked by either phentolamine (an α-adrenoceptor antagonist) or propanolol (a β-adrenoceptor antagonist). OD values of α-MT, an inhibitor of tyrosine hydroxylase, at doses of l× 10-10, 1× 10-9, and 1× 10-8 mol/L respectively were 0.71, 0.71, and 0.69, which were all notably higher than that of control (0.65, P＜0.01). NK cytotoxicity was markedly attenuated by both NE and α-MT at the three doses mentioned above (17.69 %, 17.06 %, and 16.89 % versus 25.18 % for NE; 18.85 %,18.44 %, and 17.04 % versus 23.22 % for α-MT; all P＜0.01). The suppression of NK cytotoxicity by NE was prevented by propranolol but not by phentolamine. CONCLUSION: Exogenous NE exerts a suppressive action in modulating functions of T and NK cells, with the former via both α- and β-adrenoceptor mediated mechanisms and the later mainly through β-adrenoceptors. Endogenous catecholamines synthesized by lymphocytes have also an autoregulatory effect on the lymphocytes themselves.