Harvard University (Boston, MA) and Muhmbili University (Dar es Salaam, Tanzania) have been involved in collaborative research for over 2 decades. Much of that has been on HIV infection since 1989, including examining risk factors for prevalent and incident infection among women; studying perinatal transmission; investigating psychosocial issues among infected women; and implementing intervention studies among infected women and children. Recent findings from our group include that vitamin supplements resulted in significant reductions in adverse pregnancy outcomes, reduced mortality in infected children, and improved maternal immune status; and preliminary evidence that HIV-1 subtypes have differential risk for vertical transmission. Members of our group collaborated in the UNAIDS PETRA study in which shortcourse AZT+3TC reduced perinatal transmission. In the course of these research activities, we have developed substantial infrastructure and expertise in laboratory and behavioral sciences, and epidemiology and biostatistics at Muhmbili. Our primary focus in this application is on perinatal transmission. We propose to enroll and follow up 800 HIV-infected pregnant women every year, and describe access to a much larger potential pool of positive pregnant women. Details of recruitment, randomization, follow up, retention, and psychosocial support are included. We describe our substantial experience in long term follow up, data management, high quality laboratory work, and community involvement. We also describe the strong potential for, expanding into a community-based study in prevention and treatment of sexually transmitted diseases in the Kagera region building upon 10 years of research activity on HIV and STDs in that setting. Populations of HIV-negative women that we have access to, and that could be potentially useful for examining the efficacy of microbicide or behavioral interventions, are also described. We believe that the combination of the preexisting infrastructure from ongoing studies, scientific expertise at Muhimbili and Harvard, good communications between Dar es Salaam and the U.S., the commitment of the authorities in Tanzania to HIV research, and the political stability in Tanzania, would make this collaboration a valuable addition to the HPTN.