A number of studies documented that the heavy metals are not only toxic for the organisms but they may modulate immune responses. The immunomodulatory activity was proved in several in vivo and in vitro model systems. In the current study, immunomodulatory activities of lead and cadmium are presented. The viability of both lymphocytes and macrophages was affected by heavy metals in a dose- and time-dependent manner. In the case of lead, the depression of N-oxide production closely correlated with increased blast transformation of spleen cells induced by concanavalin A (ConA). On the contrary, cadmium suppressed the production of N-oxides but stimulated significantly the proliferation of spleen cells. The production of cytokines by lymphocytes and macrophages was dependent on the in vitro model used. Generally, the treatment of macrophages with lead results in disregulation of the production of proinflammatory cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin 1alpha (IL-1alpha) and interleukin 6 (IL-6)] and preferential production of Th1 type of cytokines (IFN-gamma and IL-2). Cadmium seemed to trigger the Th2 cytokine regulatory pathway [interleukin 4 (IL-4), interleukin 10 (IL-10)]. The results suggest the metal-induced changes in immunoregulatory mechanism of host with potentially severe clinical consequences.