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The continuous presence of Auranofin (AF), 1.0 microgram/ml and above, or sodium aurothiomalate (GST), 2.0 micrograms/ml and above, inhibited the phytohaemagglutinin-induced proliferation of monocyte-depleted mononuclear cells. Preincubation of monocytes (M phi) with AF, 1.0 microgram/ml, caused a minor increase in the co-stimulatory effect of LPS-induced M phi-culture supernatants, whereas preincubation with AF 2.5 micrograms/ml and above resulted in a dose-dependent decrease in production of the co-stimulatory factor--probably interleukin-1 (IL-1). This inhibition is not due to decreased M phi viability, production of suppressive substances, or drug interference with the IL-1 test assays. A similar preincubation with GST up to 100 micrograms/ml had no effect on IL-1 production, nor did preincubation with thioglucopyranose, triethylphosphine or chloroauric acid, the three molecular sub-components of AF. The inhibitory effect of AF on the production of IL-1--as well as other co-stimulatory monokines--and on lymphocyte proliferation might explain the anti-inflammatory and disease-modifying effect of the drug.