Vermiculine, a macrocyclic aglycosidic dilactone isolated from Penicillium vermiculatum, was shown to have an inhibitory effect on the ability of concanavalin A to induce cytokine production in unseparated peripheral blood leukocytes (whole blood cultures). Vermiculine inhibited the production of (FN-gamma > IL-2 > TNF > IL-6. However ils effect on IFN-gamma and IL-2 was found to be bimodal. The suppressive effect of vermiculine was manifested at low concentrations (0.01 to 1.0 mu g/ml) of the agent and an increased production of cytokines was observed when the highest concentration of the agent (10 mu g/ml) was used. Vermiculine suppression of IFN-gamma production by unseparated leukocytes from healthy donors and from patients with rheumatoid arthritis exhibited a difference of about 2 to 20%.