Normal murine peritoneal macrophages exhibited anti-tumour cytotoxicity following simultaneous incubation with C. parvum and lymphoid cells from C. parvum-treated mice. Both T- and B-lymphocytes appear to be involved in this macrophage activation which is mediated by a soluble factor(s) released by immune lymphoid cells in response to the specific immunising strain of C. parvum. Cells capable of macrophage activation do not appear until 6 days following systemic C. parvum administration despite the appearance of cytotoxic macrophages in vivo by day 3. It was therefore concluded that two mechanisms of macrophage activation might exist (1) an early phase of activation, possibly involving a direct effect on macrophage precursors by C. parvum, and (2) a later phase in which activation is mediated by T- and B-cells responding to the C. parvum stimulus.