SummaryHuman peripheral blood monocytes from normal donors were isolated by differential centrifugation and culturedin vitroin hydrophobic Teflon–coated tissue culture bags. Cells were harvested between 0 and 10 days and tested for their ability to kill schistosomula ofSchistosoma mansoniin an in–vitro cytotoxicity assay. Freshly isolated, unstimulated monocytes demonstrated minimal cytotoxic capability. However, this was increased if the cells were pretreated with human recombinant gamma interferon (IFN–γ), or with specific anti–5.mansoniantiserum. As the monocytes maturedin vitrothere were marked increases in the levels of antibody–independent killing of schistosomula. Monocytes grownin vitrowith IFN–γ (104u/ml) took 2–3 days to develop almost maximal cytotoxicity (mean 94% kill of schistosomula). In contrast, unstimulated monocytes (no IFN–γ) took between 5 and 7 days to achieve comparable cytotoxicity (mean 99% kill). Killing of the schistosomula was dependent upon a high effector to target ratio, and was a relatively slow phenomenonin vitro, parasite attrition occurring between 17 and 36 h. Supernatants from cytotoxic macrophages were ineffective in mediating cytotoxici