Natural killer (NK) cell activity was studied in 23 patients with systemic lupus erythematosus (SLE). The overall NK activity was lower in patients with SLE than in normal female individuals. Patients with clinically active SLE disease had slightly lower NK activity than the patients with inactive disease. Other clinical parameters as well as treatment status did not correlate with NK activity. Interferon (IFN) enhanced the NK activity of normal individuals and of 11 SLE patients, while it did not enhance in the remaining 12 patients. The patients whose NK activity was enhanced by beta-IFN had significantly higher initial activity than those who did not respond to beta-IFN. Furthermore, peripheral mononuclear cells (MNC) from IFN responders produced gamma-IFN after stimulation with concanavalin A (Con A) in titres comparable to those of normals. In contrast, peripheral MNC from beta-IFN non-responders failed to produce significant titres of gamma-IFN after stimulation with Con A. These results indicate that certain patients with SLE have low NK activity, which is generally paralleled by an inability to respond to exogenous beta-IFN and by blunted production of gamma-IFN after stimulation with Con A.