Worldwide, approximately 500,000 infants are perinatally infected with human immunodeficiency virus (HIV) each year, most of whom are born in developing countries. In 1994, a clinical trial in the United States and France demonstrated that zidovudine (ZDV) administered orally five times a day to HIV-infected pregnant women starting at 14-34 weeks' gestation, intravenously during labor, and orally to their newborns for 6 weeks reduced the risk for perinatal HIV transmission by two thirds. In 1994, this regimen was recommended as standard care in the United States; however, because of its complexity and cost, this regimen has not been implemented in most developing countries, and no other intervention had been efficacious in reducing perinatal HIV transmission. In 1996, the Ministry of Public Health of Thailand and Mahidol University, in collaboration with CDC, initiated a randomized, placebo-controlled trial of a simpler and less expensive regimen of ZDV to prevent perinatal HIV transmission. This report describes preliminary trial results, which indicate that a short-term antenatal regimen of ZDV reduced the risk for perinatal HIV transmission by approximately half.