Hemolytic (complement-fixing) antibodies to single-stranded (ss) or double-stranded (ds) DNA, measured by recently developed PHL assay, occurred closely correlated with renal activity in patients with systemic lupus (SLE). Approximately one third of the patients with renal disease had hemolytic antibodies to ss-DNA but never to ds-DNA. Hemolytic antibodies were scarcely detectable in patients with mild course. Serial studies also revealed that the estimation of the hemolytic antibodies to ds- and/or ss-DNA was particularly valuable in predicting the future course of the SLE. The emergence of hemolytic antibodies to DNA may be an ominous sign suggestive of grave prognosis in SLE.