The greater resistance of HCV genotype 1infection to IFN therapy has been partially attributed tofunctional inhibition of the type 1 interferon induced antiviralprotein PKR in vitro. Whether PKR has antiviralactivity against HCV in vivo is unknown. Whilst the ultrastructurallocalisation of PKR is known in vitro, it is notdefined in chronic hepatitis C disease. Using a novelimmuno-gold technique we characterised the expression ofintrahepatic PKR protein at the ultra-structural level in fourpatients with chronic HCV disease compared to normalhuman PBMCs, HepG2 cells and a normal human liverbiopsy. All four HCV patients labelled for PKR protein,localising to the nucleus, nucleolus and cytoplasm. Nuclearlabelling was confined mainly to the nucleolus andeuchromatin. Cytoplasmic labelling was evident withinsmooth vesicles. Strong immunogold labelling was alsoevident within the cisternae of the rough endoplasmicreticulum. A similar pattern of ultra-structural nuclear andcytoplasmic PKR protein labelling was seen in PBMCsfrom healthy donors, HepG2 cells and a normal liverbiopsy. The mean nuclear and cytoplasmic count for PKRprotein in the HCV group was 21 ± 4 and 18 ± 3 goldparticles/lm2, respectively. This represented an increase,though not statistically significant, in nuclear and cytoplasmiclabelling for PKR protein in HCV biopsies relativeto normal liver tissue.