Normal and enlarged perihepatic and mediastinal lymph nodes are detectable by ultrasonography. Aim of the present study is to determine the detection rate, size, and correlation of mediastinal and perihepatic lymphadenopathy in patients with chronic hepatitis C, healthy controls, and patients with inflammatory or neoplastic mediastinal lymphadenopathy. The mediastinum and liver hilus of 89 patients with chronic hepatitis C as well as of 34 healthy volunteers and 20 patients with mediastinal lymphadenopathy of different origin with adequate sonographic visualization were screened for the number and size of lymph nodes by high resolution ultrasonography. Lymph nodes were detectable in the mediastinum of 75/89 (84%) patients with chronic hepatitis C and 22/34 (65%) healthy volunteers (total lymph node volume [LNV]: 1.0 +/- 0.8 mL versus 0.3 +/- 0.4 mL, p < 0.001). In all patients with mediastinal lymphadenopathy, the mediastinal lymph node volume was above 15 mL. In patients with chronic hepatitis C a trend could be observed, that patients with larger perihepatic lymph nodes reveal also larger mediastinal lymph nodes. High resolution ultrasonography is able to detect enlarged mediastinal lymph nodes in patients with chronic hepatitis C. Mediastinal lymphadenopathy is considered as an extrahepatic manifestation of chronic hepatitis C. In general, the mediastinal lymph node volume differs in size to patients with lymphadenopathy related to neoplasia or sarcoidosis. The mechanism of lymphadenopathy in the liver hilus and mediastinum in patients with chronic hepatitis C is yet unknown.