Cell surface components of viridans streptococci and enterococci have been shown to stimulate the release of tumor necrosis factor alpha (TNF) and interleukin-6 from monocytes/macrophages. In the sera from 10 patients with subacute enterococcal or streptococcal endocarditis, however, the levels of both cytokines were low or undetectable, with elevated TNF levels on admission in 3 patients with complicated disease. Soluble TNF receptor levels were significantly elevated compared with those of healthy controls. When patients with malaria were used as a control group of acute intravascular infection with high circulating TNF values, the ratio between soluble TNF receptors and TNF on admission was significantly greater in the patients with subacute bacterial endocarditis. Besides different amounts of circulating TNF, enhanced TNF receptor shedding may have an important role in the pathogenesis of subacute versus acute clinical disease following human intravascular infection.