The objective was to investigate herpes simplex virus (HSV) epidemiology amongst HIV-positive and HIV-negative men who have sex with men (MSM) in England and Wales. Unlinked anonymous sera from 3,968 MSM attending 12 sexual health clinics in 2003 were tested for HIV, HSV-2 and HSV-1 antibodies. Fifty-five percent of HIV-positive MSM were HSV-2-seropositive, compared to 17% of HIV-negative MSM (Adj RR: 2.14 [CI: 1.92-2.37]). Amongst HIV-positive individuals, there was no significant difference in HSV-2 seroprevalence by knowledge of HIV status or whether the HIV infection was recently acquired (determined through STARHS). HIV infection was also independently associated with HSV-1 serostatus (Adj RR 1.19 [CI: 1.14-1.24)]). Four of the twelve attendees who received a diagnosis of recurrent anogenital herpes at the clinic visit were HSV-1-seropositive but not HSV-2-seropositive at the time, although no cultures or PCR results were available to type the cause of the ano-genital presenting disease. It is of concern that one in two HIV-positive MSM and one in six HIV-negative MSM may be infected with HSV-2, given increasing evidence of its impact on HIV progression, onward transmission and acquisition. To date results have been disappointing from trials aimed at reducing HIV onward transmission and HIV acquisition using HSV antiviral medication. However, recent research in an African context demonstrates the efficacy of HSV antivirals in delaying HIV progression. The high prevalence of HSV-2 amongst HIV-positive MSM suggests that an increased focus on HSV control in the management of HIV amongst MSM in the United Kingdom may be warranted. Given this and existing research on the high prevalence of genitally acquired HSV-1 amongst MSM in the UK, further research is also warranted into the role of HSV-1 in the HIV epidemic in this context.