Mother-to-child transmission of HIV-1 afflicts hundreds of thousands of children every year, especially in parts of the world such as sub-Saharan Africa, where HIV infection is prevalent and resources are limited. This tragic reality has spurred researchers to search for an effective, safe, and inexpensive treatment that could reduce the risk of perinatal HIV transmission. The HIVNET 012 trial was designed to provide preliminary information on the comparative safety and efficacy of two relatively simple and inexpensive short courses of oral antiretroviral treatment likely to be feasible in resource-limited settings. The resulting report identified some problems with procedures and documentation, but concluded that these issues did not compromise the results of the study. However, these issues have led to public scrutiny and continued controversy. Review of the HIVNET 012 Perinatal HIV Prevention Study critically and objectively evaluates the study's design and conduct, and assesses the impact of the initial procedural issues on the validity of the overall findings and conclusions of the trial.