The feline leukemia virus (FeLV) disease model was used to conduct a toxicity and antiretrovirus efficacy trial of dextran sulfate (DS; molecular mass, 7,000 to 8,000 Da). In vitro, FeLV infection of feline lymphoid cells was inhibited by 10 micrograms of DS per ml. DS was administered to cats by continuous intravenous infusion at doses of 600, 120, 24, or 4.8 mg/kg of body weight per day, beginning 24 h before FeLV challenge. Doses of 24 mg/kg/day and more were excessively toxic, causing intestinal lesions and death. Similar changes were observed in unchallenged animals receiving 24 mg/kg/day, indicating that toxicity was DS mediated. The dosage of 4.8 mg/kg/day was subtoxic but did not prevent the induction and persistence of FeLV viremia. The results demonstrate that DS by continuous intravenous infusion is excessively toxic at high doses and ineffective at preventing FeLV infection at a subtoxic dose in the FeLV cat model.