Spleen cells from mice bearing progressively growing syngeneic methylcholanthrene-induced sarcomas are immunologically hyporeactive and also their proliferative responses to interleukin-1 (IL-1) or interleukin-2 (IL-2) stimulation are considerably decreased. The hypo-reactivity to IL-2, but not to IL-1, is due to an active suppression: spleen cells from tumour-bearing mice inhibit the IL-2-induced proliferation of cells from normal donors. Supernatants obtained after cultivation of spleen cells from mice bearing tumours show similar suppressive effects. The hyporeactivity to IL-2 and IL-1 in tumour-bearerers is not improved by indomethacin, an inhibitor of prostaglandin synthesis. The results show that the low reactivity to IL-2 in tumour-bearing mice is due to an active suppression mediated by spleen cells and their factor(s) and that more different mechanisms regulate responsiveness to interleukins in tumour-bearing hosts.