The intrahepatic expression of interleukin (IL)-1beta 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-1beta and TNF-alpha immunoreactivity was predominantly localized in sinusoidal cells, with IL-1beta 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-1beta 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-1beta 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-1beta production by sinusoidal cells in chronic hepatitis C, which might facilitate viral persistence.