Antibody-sensitized line-1 or line-10 tumor cells treated with GPC have previously been shown to incorporate increased amounts of acetate, glycerol, or fatty acids into complex lipids compared with control cells within 10 min after the addition of GPC to the cells; the release of lipid from these cells was also enhanced at this time interval. In the present study, the specific lipid moieties synthesized and released by the cells in response to incubation with antibody plus C have been identified. Antibody-GPC-treated cells uniformly synthesized and released increased amounts of the phospholipid, cardiolipin. Modifications in the synthesis and/or release of triglycerides, phosphatidyl ethanolamine, phosphatidyl choline, cholesteryl esters, or phosphatidyl serine were also observed in line-1 or line-10 cells prelabeled with a particular precursor of lipid synthesis. Treatment of antibody-sensitized tumor cells with HuC did not cause an increase in the incorporation of acetate, glycerol, or fatty acids into lipids, but caused a shift in lipid synthesis from cardiolipin to phosphatidyl choline. The cells treated with antibody plus HuC released increased amounts of cholesteryl esters and triglycerides. These data suggest that 1) GPC and HuC may act at different sites on the cell; 2) the mechanism whereby these tumor cells can resist killing by GPC and not HuC may involve replacement of membrane-associated macromolecules (a part of which, at least, appears to be lipid) released as a result of C action; and 3) antibody-C attack stimulates several pathways of lipid synthesis (i.e., acylation as well as assembly of fatty acids and glycerol into complex lipids).