To study the potential role of tumor necrosis factor (TNF) in chronic heart failure, we measured the plasma levels of TNF by enzyme linked immunoabsorbent assay in 109 patients with various heart diseases grouped as 'non-heart failure' (n = 36), 'heart failure' (n = 36) and 'cachectic' (n = 37). The daily food intake was also investigated. The results showed that there was no obvious difference of daily caloric intake among the three groups of patients. Plasma levels of TNF were significantly elevated in the patients with 'heart failure' (0.51 +/- 0.26 ng/ml, mean +/- S.E.M.), and even higher in the patients with 'cachexia' (6.19 +/- 2.76 ng/ml), as compared with the patients with 'non-heart failure' (0.09 +/- 0.03 ng/ml). Twenty-five patients with 'cachexia' and 11 patients with 'heart failure' had plasma levels of TNF > or = 100 pg/ml, whereas only 5 patients with 'non-heart failure' had plasma levels of TNF above that level. The patients with high levels of TNF were more cachectic than those with normal levels of TNF (body mass index 19.5 +/- 3.4 vs. 22.3 +/- 3.6, P < 0.05). In multivariate analysis, elevated levels of TNF were associated with the level of serum total protein, presence of heart failure and cachexia. These findings indicate that plasma levels of TNF are increased in patients with heart failure, and high levels of TNF may play an important role in the pathogenesis of cardiac cachexia.