OBJECTIVE: The purpose of this study was to assess the risk of perinatal HIV-1 transmission in women who are coinfected with herpes simplex virus-2 (HSV-2). STUDY DESIGN: We performed a nested case-control study of 26 women whose HIV-1 was transmitted to their infants and 52 control subjects whose HIV-1 was not transmitted. We assessed antepartum serologic evidence of HSV-2 by HSV-2 serostatus and genital tract evidence of HSV-2 by presence of HSV-2 DNA. RESULTS: There was no significant association between antepartum serologic evidence of HSV-2 coinfection and the risk of perinatal HIV-1 transmission. There was also no association between antepartum genital tract evidence of HSV-2 coinfection and risk of perinatal HIV-1 transmission. CONCLUSION: Women who were infected with HIV-1 with antepartum serologic and genital tract evidence of HSV-2 coinfection did not appear to have an increased risk of perinatal HIV-1 transmission. However, further investigations are needed to assess HSV-2 reactivation and the risk of perinatal HIV-1 transmission at the time of delivery.