INTRODUCTION: Epidemiologic links between herpes simplex virus type-2 (HSV-2) and hepatitis C virus (HCV) exist but are poorly characterized. Seroprevalence studies of HSV-2 in veteran populations with chronic HCV infection are lacking. METHODS: The authors reviewed the medical histories and results of the HerpeSelect IgG (Focus Diagnostics, Cypress, CA) of 244 HCV-infected male veterans engaged in care. All patients were human immunodeficiency virus negative and >99% defined themselves as heterosexual. RESULTS: Using the manufacturer's recommended cutoff for positive results (>1.1), 51.5% of HCV-infected veterans were seropositive for HSV-2. When increasing the cutoff to >3.5, 38.7% of persons were seropositive for HSV-2. Reports of previous diagnosis with genital ulcer disease (9/213; 4.3%) or genital herpes (4/213; 1.9%) were rare. CONCLUSIONS: HSV-2 infection commonly occurred in the study sample of HCV-infected veterans but was infrequently recognized. Future studies should optimize the use of type-specific serologic screening tests in HCV-infected persons. The high prevalence of HSV-2 in this population merits further investigation into any potential biologic interactions between these common viral infections. Copyright © 2012 Southern Society for Clinical Investigation.