The intrahepatic expression of interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha was studied in liver specimens from patients with chronic hepatitis C (n = 29) and primary biliary cirrhosis (PBC; n = 12) and from normal controls (n = 19), IL-1 beta and TNF-or immunoreactivity was predominantly localized in sinusoidal cells, with IL-1 beta immunoreactivity being weaker in chronic hepatitis C samples than in PBC or control samples, whereas no difference in staining intensity could be observed for TNF-alpha, On semiquantitation by reverse transcription/ competitive polymerase chain reaction, IL-1 beta mRNA levels were significantly lower in chronic hepatitis C than in PBC or control samples (chronic hepatitis C, 0.87 +/- 0.77; PBC, 7.96 +/- 3.32; control, 3.78 +/- 2.56 amole IL-1 beta mRNA/fmole beta-actin mRNA; P<.001). In contrast, no significant differences in TNF-alpha mRNA levels were observed between the groups. The data suggest insufficient IL-1 beta production by sinusoidal cells in chronic hepatitis C, which might facilitate viral persistence.