A variant cell line of Leishmania donovani (named R2D2) has been selected for resistance to the cytotoxic lectin ricin agglutinin and shown to be defective in the synthesis of its major glycoconjugate lipophosphoglycan. Compared to the parental line, R2D2 cells showed a marked resistance to the toxic effects of ricin and an increased sensitivity toward concanavalin A. The synthesis of lipophosphoglycan by R2D2 cells was judged to be less than 1% relative to that of wildtype cells as determined by incorporation of radioactive mannose and galactose and by electrophoretic and chromatographic analyses. Although lacking lipophosphoglycan, R2D2 parasites were capable of infecting cultured U937 macrophages.