This study compared B lymphocytes isolated from different tissues with regard to their proliferation, apoptosis and the effects of cortisol on these processes. B-lymphocytes, isolated from the head kidney and spleen, were characterised by higher proliferation and lower intracellular calcium (Ca2 i) response to Ig-crosslinking compared with peripheral blood B-lymphocytes. Cortisol induced high levels of apoptosis (160% of control levels) in peripheral blood B-lymphocytes, in combination with a stimulatory (LPS) signal. Head kidney and to a lesser extent spleen B-lymphocytes, although less sensitive than their equivalent in peripheral blood, underwent cortisol-induced apoptosis irrespective of extra stimulation up to 150% of control levels. Also proliferation with and without LPS stimulation was suppressed by cortisol. In view of the relatively modest concentration of cortisol (compared to plasma values measured during stress conditions) that is effective in inducing a significant increase in apoptosis in all three populations of B-cells, it is suggested that cortisol may be important for immunoregulation in both stressed and non-stressed conditions. This implies possible severe impact of stress on lymphocyte development and activity. Different sensitivity of B-cells to the corticosteroid, with respect to developmental stage and activity, may prevent excessive and long lasting depletion of B-lymphocytes.