Background: Male circumcision is protective against human immunodeficiency virus (HIV) and select other STIs. The protective role of male circumcision in genital herpes simplex virus (HSV) infection and disease, however, remains controversial. Methods: We evaluated data from a sample of heterosexual black men attending a sexually transmitted diseases clinic to determine if circumcision status influenced HSV-1 and HSV-2 seroprevalence, clinical genital disease, or asymptomatic shedding. Consenting participants answered questionnaires detailing sexual history, then underwent a focused physical examination, serological testing for HSV-1 and HSV-2, and collection of genital swabs for virus detection. Univariate and multivariate analyses were performed to assess the relationship of circumcision status to HSV seroprevalence. Results: Of 460 men, 335 (73%) were circumcised and 125 (27%) were not circumcised; 61% were HSV-1 positive and 46% were HSV-2 positive. HSV-2 seroprevalence did not signiicantly differ between circumcised and uncircumcised men. However, uncircumcised men had a signiicantly higher HSV-1 seroprevalence than circumcised men (OR: 1.85; CI: 1.15-2.96). This difference in seroprevalence occurred only in men between 18 and 25 years of age (OR: 2.83; CI: 1.38-5.83) with men over 26 years of age having similar HSV-1 seroprevalence. Lack of circumcision remained independently associated with higher HSV-1 seroprevalence after adjusting for age, years since sexual debut, and lifetime number of sexual partners. For both groups, 20% of men had genital lesions on physical examination. Of circumcised and uncircumcised men with genital lesions, 33% and 31% were actively shedding HSV-1 or HSV-2 from lesions, respectively. Asymptomatic HSV shedding was observed in 12 participants, all of whom were circumcised. Conclusions: Lack of male circumcision is associated with higher HSV-1, but not HSV-2, seroprevalence in young black heterosexual men. Copyright © 2010 American Sexually Transmitted Diseases Association. All rights reserved.