The aim of this study is to evaluate the association between hepatoduodenal lymphadenopathy, detected by transabdominal ultrasound (US), and HCV-related chronic hepatitis, and to determine if their presence and size correlate with biochemical and/or histological activity including the presence or absence of liver cirrhosis.The study included 77 anti-HCV antibody positive, HbsAg negative patients presenting to the Tropical Medicine Department, Faculty of Medicine, Cairo University. Sixteen healthy volunteers participated in the study as control subjects. Adequate visualization of the area of the hepatoduodenal ligament was achieved by US in 72 patients (93.51%) and in all control subjects (100%). Hepatoduodenal lymph nodes were detected in 68 of the 72 patients (94.44%) and in 7 of the 16 control subjects (47.75%) and the difference was highly significant (p<0.01). There was also a highly significant difference in the number and size of lymph nodes between patients and control subjects (p<0.01).There was a significant positive correlation between total perihepatic lymph node volume and serum bilirubin level, AST, ALT, ALP and GGT. There was a highly significant difference in the total perihepatic lymph node volume, and a significant difference in the biggest lymph node volume between PCR positive and negative patients. There was also a significant positive correlation between the biggest lymph node volume and the level of viremia. On histopathological examination of liver biopsy specimens, there was a significant positive correlation between total perihepatic lymph node volume and biggest lymph node volume with the grade of activity, and a highly significant positive correlation between the longest axis of the biggest lymph node and the grade of activity. A significant positive correlation was found between lymph nodes size and stage of fibrosis, and the mean total perihepatic lymph node volume and biggest lymph node volume were significantly higher in patients with cirrhosis than those without. It was concluded that hepatoduodenal lymph nodes can readily be detected by transabdominal US in patients with chronic hepatitis C and their enlargement reflects the activity of the liver disease.