Natural killer (NK) cell activity and its stimulation by interferons (IFNs) and interleukin-2 (IL-2) are diminished in Sjögren's syndrome and systemic lupus erythematosus (SLE). Serum samples of these patients often contain circulating immune complexes, which may influence NK cell activity. Sixteen patients with Sjögren's syndrome (14/16 immune complex positive), 14 with SLE (9/14 immune complex positive), and 11 controls (immune complex negative) were studied. Mononuclear cells collected from a Percoll gradient were preincubated with recombinant IFN-alpha (rIFN-alpha) (100 U/ml), rIFN-gamma (1000 U/ml), rIL-2 (100 U/ml), or without cytokine. Natural killer cell activity was determined by incubating the mononuclear cells with carboxyfluorescein labelled K562 cells, and the percentage decrease of fluorescence was measured on an FACS Analyzer. In patients with Sjögren's syndrome and SLE NK cell activity and the numbers of cells expressing the NK cell associated antigens CD16 and Leu7 were diminished compared with the controls. Interleukin-2 stimulated NK cell activity significantly in comparison with the non-stimulated value in all studied groups, whereas IFN-gamma only stimulated NK cell activity in both patient groups and IFN-alpha only in patients with Sjögren's syndrome. There was no correlation between NK cell activity, with or without stimulation, and the immune complex concentrations. It is concluded that NK cell activity is decreased in Sjögren's syndrome and SLE and that it may be partially restored by IL-2 and IFN-gamma in both diseases, and by IFN-alpha in Sjögren's syndrome. The decrease of NK cell activity did not correlate with immune complex concentrations; on the other hand, decreased numbers of NK cells (CD16+ or Leu7+) and of cytokine concentrations might be important in the impaired NK cell activity in both diseases.