Plasma tumour necrosis factor alpha (TNF) and in-vitro TNF production by peripheral blood mononuclear cells (PBMC) were studied in 22 HBsAg seropositive patients and compared with 23 normal and 10 disease controls. Plasma TNF and unstimulated TNF production correlated (Rs = 0.55, p = 0.012) and were significantly elevated in HBsAg and HBeAg seropositive patients (p less than 0.001, p = 0.006) compared with normal controls. TNF production was also elevated in these patients when PBMC were stimulated with interferon-gamma (p less than 0.05) or LPS (p = 0.035). Plasma TNF and TNF production in HBsAg anti-HBe seropositive subjects were not elevated. TNF production in unstimulated cells correlated with serum HBV DNA level (R = 0.53, p = 0.02) but not with serum aspartate transaminase (AST) or histological activity. It is concluded that PBMC are activated to produce TNF both spontaneously and in response to second stimuli in chronic hepatitis B virus infection and that this activity is related to the presence of viral replication.