Many relapses of systemic lupus erythematosus (SLE) are preceded by a rise in antibodies against double-stranded DNA (anti-dsDNA). We investigated whether these relapses can be prevented by giving prednisone when a rise in anti-dsDNA occurs. 156 patients with SLE were studied. Anti-dsDNA was measured by Farr assay monthly. When a rise in anti-dsDNA was found, patients were randomly assigned either conventional treatment or 30 mg prednisone added to the current daily dose and tapering off to baseline over 18 weeks. A rise in anti-dsDNA was detected in 46 patients (24 assigned conventional treatment and 22 prednisolone). The relapse rate was higher in the conventional group than in the prednisolone group (20 vs 2, p < 0.001). Although rises in anti-dsDNA in the prednisone group were treated with additional prednisone, the cumulative oral doses of prednisone in the two groups did not differ significantly (p = 0.025). 7 major relapses requiring additional cytotoxic immunosuppressive treatment occurred in the conventional group versus 2 in the prednisone group. Treatment with prednisone as soon as a significant rise in anti-dsDNA occurs prevents relapse in most cases, without increasing the cumulative dose of prednisdone given.