The effects of Nigella sativa (N. sativa) seeds and their soluble fractions were studied in vitro on lymphocyte response to different mitogens and on polymorphonuclear leukocyte phagocytic activity. No stimulatory effect of N. sativa was detected on lymphocyte response to phytohemagglutinin, concanavalin-A or pokeweed mitogen. A stimulatory effect of N. sativa was noticed on the lymphocyte response to pooled allogeneic cells. This effect was more pronounced when the low molecular weight (< 10 kDa) fraction was used and varied from one normal individual to another (25% to 825%). N. sativa enhanced the production of interleukin-3 by human lymphocytes when cultured with pooled allogeneic cells or without any added stimulator. N. sativa did not, however, enhance or suppress interleukin-2 secretion by mitogen activated peripheral blood mononuclear cells. Interestingly, N. sativa increased interleukin-1 beta, suggesting therefore, that it has an effect on macrophages. It also suppressed the leukocyte chemiluminescence activity using phorbol myristate acetate and Zymosan as stimulants. No effect of N. sativa or its fractions was, however, noticed on bacterial phagocytosis or killing when Staphylococcus aureus was used, indicating that the decrease in chemiluminescence activity in the presence of N. sativa is not relevant to the bactericidal activity.