Serum interferon levels were estimated in 67 samples obtained from 47 patients with SLE. Levels were increased in 70% of the samples and 72% of the patients. In the patients with active disease 81% had increased interferon levels, while in the group with clinically quiescent disease 10% had increased levels. In 20 patients retested 3 1/2 months after treatment the changes in interferon levels tended to parallel the changes in clinical disease activity in 80% of cases. Patients with active skin lesions, arthritis, and renal or haematopoietic involvement tended especially to have increased interferon levels. Interferon levels were directly related to ANA titre and inversely related to serum C3 levels, but not related to serum levels of circulating immune complexes or immunoglobulin. The interferon was shown to be of type alpha. The interferon level can be regarded as one of several parameters reflecting disease activity and may also be related to the prognosis. As it is possible that interferon may be a direct mediator of the pathophysiology of auto-immune disease, we do not recommend the use of interferon or its inducers in the therapy of SLE.