Cardiac myxoma cells produce large amounts of interleukin (IL)-6 and IL-8. To determine whether immunosuppressive agents could be used to treat cardiac myxoma, we tested the effects of dexamethasone and three of the newer second-generation immunosuppressive drugs, cyclosporin A, tacrolimus, and deoxyspergualin, on the production of IL-6 and IL-8 in these cells. Cultured cardiac myxoma cells were used as in vitro model of cardiac myxoma. Cells were tested for 24 hours with 10 (-7) M dexamethasone, 10 (-6) M cyclosporin A, 10 (-8) M tacrolimus, and 10 (-6) M 15-deoxyspergualin, with aliquots of conditioned medium being assayed for cytokine levels at 0, 6, 12, and 24 hours. Cardiac myxoma cells isolated from 4 patients all produced quantities of IL-6 and IL-8. The concentrations of IL-6 in the medium after 7 days in culture ranged from 79,000 to 2,740,000 pg/ml, and the concentrations of IL-8 ranged from 40,000 to 1,000,000 pg/ml. Exposure of cyclosporin A and dexamethasone almost completely inhibited the production of IL-6 and IL-8 after 24 hours of treatment. Tacrolimus inhibited the production of both cytokines by 55%, while 15-deoxyspergualin reduced IL-6 levels by 24% and IL-8 levels by 48% after separate 24 hour treatments. These results suggest that these newer immunosuppressive agents may be useful in reducing the production of IL-6 and IL-8 in patients with cardiac myxoma.