Natural killer (NK) cell activity and its stimulation by interferons (IFNs) and interleukin-2 (IL-2) are diminished in Sjogren'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 Sj6gren'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-a (rIFN-a) (100 U/mi), rIFN-y (1000 U/mi), rIL-2 (100 U/mi), 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 Sj6gren'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 sinificantly in comparison with the non-stimulated value in all studied groups, whereas IFN-y only stimuated NK cell activity in both patient groups and IFN-a only in patients with Sj6gren'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 deoreased in Sj6gren's syndrome and SLE and that it may be partially restored by IL-2 and IFN-y in both diseases, and by IFN-a in Sj6gren's syndrome. The decrease ofNK 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.