Freshly isolated human peripheral blood monocytes inhibited the growth of blood-stage asexual Plasmodium falciparum parasites in vitro. The monocytes contained intracellular parasite pigment and a few whole parasites, but the remaining parasites reinvaded fresh red cells successfully and were morphologically normal. Anti-parasitic activity of these macrophages was not significantly enhanced by treatment with recombinant tumour necrosis factor alpha, recombinant gamma-interferon or lymphoblastoid alpha-interferon. Catalase had no effect on this parasite inhibition, suggesting a hydrogen peroxide independent mechanism. Anti-parasitic activity was, however, enhanced by prior maturation of the monocytes. Monocytes matured for 6 days caused 100% killing of parasites. In contrast to identical concentrations of freshly isolated monocytes the parasites incubated with these matured macrophages showed intraerythrocytic death similar to the crisis forms seen in vivo. gamma-interferon present either during the assay or as a pretreatment had no significant enhancing effect on the killing, although cytotoxicity to tumour cell lines was enhanced. Conditioned medium from macrophages showed only moderate parasite inhibition.