Although genital herpes simplex virus (HSV) infections occurring during pregnancy are known to be associated with neonatal and maternal complications, their frequency and contributing risk factors are not well understood. We prospectively followed 29 patients who acquired genital herpes during pregnancy, to evaluate the perinatal effects of the infection. The patients were classified on the basis of clinical or serologic criteria. Fifteen patients had a primary first episode of genital HSV Type 2 (HSV-2), and 14 had a nonprimary first episode. Although no patient had disseminated disease, 6 of the 15 with primary genital herpes but none of 14 with nonprimary first-episode infection had infants with serious perinatal morbidity (P less than 0.01). Four of the five infants whose mothers acquired primary HSV-2 in the third trimester had perinatal morbidity such as prematurity, intrauterine growth retardation, and neonatal infection with HSV-2. Perinatal complications occurred in one of five infants whose mothers acquired primary HSV-2 during the first trimester, as well as in one of five infants whose mothers had primary HSV-2 during the second trimester. Asymptomatic cervical shedding of HSV-2 was detected at 10.6 percent of weekly visits made after a primary first episode, as compared with 0.5 percent of visits after a nonprimary first episode (P less than 0.01). We conclude that infants born to women who acquire primary genital herpes during pregnancy are at high risk of exposure to HSV, either during premature labor at the time of the primary episode or subsequently because of asymptomatic cervical shedding of the virus. The 40 percent incidence of serious perinatal morbidity in such women suggests that studies of preventive measures such as the use of antiviral chemotherapy are warranted.