From 1999 to 2001, the overall prevalence of resistance in the antiretroviral (ART)-naive population in St. Louis, Missouri, was 17%. We sought to determine if resistance testing in ART-naive HIV-positive pregnant women identified resistant mutations, which would modify our initial choice of therapy. A retrospective chart review was performed on all HIV-positive pregnant women seen from January 2000 to December 2001 at a university hospital. There were 72 pregnancies. Twenty-seven of 72 patients were ART naive. Genotype testing was performed in 18 of 27 naive patients. Three of 18 ART-naive patients (17%) had primary resistance (95% CI: 4%-41%) by genotype to NNRTIs. The primary mutation, G190S, conferring resistance to NNRTIs was present in 1 patient. Another had the K103N mutation. One had the K103R mutation, which conferred phenotypic resistance to NNRTIs by 8.3-fold, warranting a change in the initial regimen. In our community, resistance testing in ART-naive pregnant patients is warranted. Switching later to a more complex regimen during pregnancy may adversely affect adherence, resulting in virologic failure. Strategies to avoid prescribing a suboptimal regimen include waiting to initiate ART until the resistance testing results are available and/or beginning ART with a protease inhibitor-based regimen if the patient is already in the third trimester of pregnancy at the time of her initial clinic presentation.