Drugs and chemicals containing multiple reactive carbonyl groups have been postulated to produce nonimmunologic positive direct antiglobulin tests (DATs) both in vitro and in vivo. Suramin sodium, a reverse transcriptase inhibitor that was under investigation as a potential treatment for human immunodeficiency virus infection, has six reactive carbonyl groups. Because of suramin's chemical structure, it was hypothesized that the drug might cause a positive DAT in vitro and possibly in vivo. Suramin was found to produce a positive DAT in vitro at concentrations of 2100 mg/L or greater but did not cause a positive DAT in five patients with acquired immunodeficiency syndrome who were treated with suramin, probably because the serum levels of suramin were too low in these patients (peak therapeutic blood levels ranged from 171 to 443 mg/L).