The proposal aims at addressing the burden of disease, risk factorsfor and potential to intervene against neonatal and maternalperi-partum sepsis in a developingcountry setting with a high prevalence(29%)of maternal HIV infection. The study site is a secondary-tertiary hospital in Johannesburg, South Africa. The primary aim of this proposal is to complete a currently underwaydouble-blind randomizedplacebo controlled trial studying the efficacy of chlorhexidine (0.5% solution) intavaginal washes during labor in the mother and subsequentcleansing of the newborn with full-body chlorhexidine wipes, to prevent early -onset (within 72 hours of birth) neonatal sepsis and peri-partum (within 14 days of birth) sepsis in the mother. Based on an estimatedincidence rate of 30 cases of sepsis/1000 life births occuring within 72 hours of birth, we proposeto randomise 8 000 women during labor into one of two arms (chlorhexidine vs. autoclaved tap- water inetnmittent vaginal washes) to detect at least a 40% reduction in the incidence of neonatal sepsis, with 80% power and 95% confidence. The study-outcome measureof neonatalsepsiswill include culture confirmed disease and/or a clinical diagnosis of sepsis based on an algorithm that has been agreed upon by experts in the field. We also plan to measure in a subset of mother-infant pairs the prevalence of vaginal colonisation by bacteria in the mother during labor and the impact of the study-intervention on the incidence of colonisation of the newborn with vaginal bacterial flora. The study will evaluate the effect of the intervention on the incidence of the following specificoutcomes: Primary objectives: 1. Early (within 72 hours of birth) microbiologiocally confirmed and/ or clinically diagnosed neonatalsepsis. 2. Decrease in vertical transmission of colonization with Group B Streptococcus from the mother to the newborn. Secondary objectives: 1. Incidence of community-acquired neonatal sepsis/meningitis between72 hours and 28 days of life. 2. Incidence of peripartum culture-confirmedor clinically diagnosed maternal sepsis within 14 days fo birth. 3. Incidence of colonization of the newbornwith Klebsiela pneumoniaeand E . coli. 4. The burden of disease and risk factors for maternal peripartum infection and serious neonatal infections in SouthAfrica with emphasis on the impact of maternalHIV infection on these outcomeswill also be studied. Relevance: The findings from this study may contribute in sari to realising one of the Millenium goals of the United Nations; i.e. to halve childhood mortality by2015.The leading cause of neonatal deaths, which contribute to at least one-third of all infant deaths, in developingcountries are sepsis and birth asphyxia. Logistical and resource constraints in developing countries prohibit the implementation of strategies that have been successfully in developed countries to reduce neonatal sepsis, therefore a more practical and affordable solution is required for developing countries.