We studied the in vitro action of gold sodium thiomalate (GSTM) and Methotrexate (MTX) on spontaneous and lipopolysaccharide (LPS) stimulated TNF alpha production by peripheral blood mononuclear cells (PBMC) of patients with rheumatoid arthritis (RA) and normal healthy individuals. GSTM and MTX (10 microg) each were added to the cultures of PBMC either in medium alone (spontaneous) or in the presence of 10 microg of LPS. GSTM and MTX augmented spontaneous TNF alpha production in normal individuals and patients with RA but did not influence LPS stimulated TNF alpha production. However, TNF alpha production by the PBMC of normal individuals was inhibited if the PBMC were stimulated with LPS, for 6 or 12 h, washed to remove LPS and subsequently incubated with GSTM. These data indicate that GSTM can inhibit TNF alpha production when the PBMC are preactivated by LPS.