We sought to clarify the incidence and role of Helicobacter pylori (H. pylori) seropositivity in patients with hepatitis C virus (HCV) infection and the effect of coinfection on interferon-alpha and ribavirin therapy. The presence of H. pylori was tested using a commercially available enzyme immunoassay in serum samples from 93 patients with chronic hepatitis C. Clinical features, HCV markers and response of HCV to interferon-alpha and ribavirin were compared between H. pylori-positive and H. pylori-negative patients. Anti-H. pylori antibody was detected in 45 (48%) of the 93 patients, whose median HCV-RNA level (495 vs 760 kIU/mL; P = 0.013) and platelet count (128 vs 158 x 10(3)/microL; P = 0.009) were significantly lower than in patients with HCV infection alone. Anti-H. pylori antibody levels were found to be significantly correlated with fibrosis score (P = 0.0083, r = 0.33) but inversely related to platelet count (P = 0.0037, r = -0.34). The sustained response rate for HCV clearance following interferon-alpha and ribavirin treatment did not differ between patients with and without anti-H. pylori seropositivity. The presence of H. pylori [odds ratio (OR) 8.61; 95% confidence interval (CI) 1.59-46.70] and fibrosis score (OR 30.13; 95% CI 5.44-166.78) were found by multivariate analysis to be associated with the decrease of platelet count during therapy. Coexistent H. pylori infection does not demonstrably influence the clinical course of chronic hepatitis C. A possible connection between H. pylori coinfection and thrombocytopenia was found during the treatment course, suggesting that preemptive eradication of H. pylori may facilitate completion of treatment and increased sustained virological response.