Previous work has shown that proteins can be nondestructively delivered into the cytoplasm of folate receptor-bearing cells if the proteins are conjugated to folic acid prior to addition to cells. In view of other reports suggesting the membrane receptor for folic acid is vastly overexpressed on tumor cells, we decided to explore whether malignant cells might be selectively targeted in a co-culture with nontransformed cells using ligated folate as the targeting agent. Exploiting the cytotoxicity of the ribosome-inactivating toxin, momordin, to assay successful intracellular protein delivery, we demonstrate that HeLa and KB cells (two malignant human cell lines) can be selectively and quantitatively killed in co-cultures with WI38 and Hs67 cells (two normal human cell types). Not only are the normal cells not damaged by treatment of the co-cultures with momordin-folate, but their rates of proliferation actually accelerate, presumably due to increased availability of nutrients otherwise consumed by the transformed cells. Analysis of folate receptor number before and after momordin-folate treatment indicates that receptor density may be a good predictor of toxin-folate sensitivity. Taken together, the data suggest that conjugates of folic acid with cytotoxic proteins warrant further examination as possible tumor-specific chemotherapeutic agents.