Tumour necrosis factor (TNF) was detected in scrum from mice challenged with Paracoccidioides brasiliensis. The scrum TNF levels of mice challenged with an avirulent strain were significantly higher than those of mice challenged with a virulent strain, and the same was observed for the TNF levels of mice challenged with a cell wall fraction (F1) from the two fungal strains. Fraction F1 consisted of chitin and β-glucan; but although the chitin contents were similar for the two strains, the avirulcnt strain allowed a greater content of β-glucan. The β-glucan, purified from both strains, increased serum TNF levels in an identical dose-dependent manner, whereas purified chitin did not induce scrum TNF levels. P. brasiliensis, the F1 fractions and β-glucan induced macrophages to secrete TNF in vitro. The differences in TNF levels, induced by the different fungal strains, were correlated with the β-glucan concentrations in the cell walls of both the avirulent and virulent strains of P. brasiliensis. These findings support a role for TNF in the pathogenicity of P. brasiliensis.