The Antiretroviral Pregnancy Registry (APR) is an ongoing international prospective exposure-registration cohort study that monitors outcomes of pregnancies exposed to marketed antiretroviral medications. The population of women exposed to antiretrovirals remains relatively small, which limits the power of the registry. In order to maximize identification of a teratogenic signal, a special birth defect classification system was devised. Birth defects were organized based upon organ system and embryology, using the Metropolitan Atlanta Congenital Defects Program as a model. Grouping defects that share embryology and pathogenesis increases the likelihood that a teratogenic effect will be apparent. The result is a three-tiered system: organ system, preferred defect term, and reported defect term. This system is text based, which eliminates the need to memorize codes and allows use by anyone familiar with medical terminology. Once established, the new APR Organ System Classification retains enough flexibility that categories may be collapsed or expanded as experience grows. Standardized nomenclature also minimizes variation introduced by collecting defect reports from many different sources. Copyright © 2002 John Wiley & Sons, Ltd.