Single cell analysis with capillary electrophoresis, a technique capable of detecting zeptomole quantities (10(-21) mole) of neurochemical species, has been used to demonstrate that lymphocytes are capable of active synthesis of dopamine and norepinephrine. Exposure of lymphocytes to catecholamines at concentrations as low as 10 nM leads to decreased proliferation and differentiation, e.g. interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and immunoglobulin (Ig). In addition, both inhibition of dopamine uptake with nomifensine and inhibition of packing of catecholamines into vesicles with tetrabenazine, results in significantly lower levels of dopamine and norepinephrine (p < 0.01 and p < 0.05, respectively). The catecholamine-dependent inhibition of T- and B-lymphocyte activity is mediated via an induction of a Bcl-2/Bax and Fas/FasL involved apoptosis. These findings indicate a novel mechanism for regulation of lymphocyte activity in the central nervous system, whereby elevated regional levels of catecholamines might lead to the immunoprivilege of the brain.