Flounder B lymphocytes isolated from different tissues were studied in terms of cell proliferation, apoptosis and the effects of cortisol on these processes. B lymphocytes, isolated from the flounder head kidney and spleen, were characterized by higher proliferation and lower intracellular calcium ($Ca^2$) response to lgcrosslinking compared with peripheral blood B lymphocytes. Cortisol induced high levels of apoptosis (150% 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 142% of control levels. Also proliferation with and without LPS stimulation was suppressed by 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, suggesting 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.