We report the development of a severe polyneuropathy in 4 of 38 patients who were receiving parenteral suramin therapy for the treatment of various underlying malignancies. In 2 of these patients, the neuropathy progressed to generalized flaccid paralysis with bulbar and respiratory involvement, requiring endotracheal intubation and ICU monitoring. EMG and nerve conduction studies showed evidence of conduction block, suggestive of a demyelinating polyneuropathy. After several weeks, both patients improved clinically. The other 2 patients developed a reversible neuropathy with flaccid paresis of the limbs but without bulbar or respiratory compromise. No immediate response to plasmapheresis was noted. All 4 patients demonstrated an elevated CSF protein in the acute phase of their neuropathy, which declined or returned to normal during recovery. The development of polyneuropathy correlated with the maximum plasma suramin level, with an estimated 40% risk of developing neurotoxicity in those patients whose maximum level was 350 micrograms/ml or greater. No correlation could be made with the total dose of suramin administered or with the duration of therapy. Two of these 4 patients manifested tumor shrinkage while receiving suramin therapy. We conclude that suramin, a promising antineoplastic agent, is capable of inducing a severe sensorimotor polyneuropathy which appears to be related to the plasma concentration of suramin. Serial measurement of the plasma concentration during suramin therapy is recommended.