Studies comparing placental pathology between human immunodeficiency virus (HIV)-positive and HIV-negative patients have shown conflicting results. In addition, few studies have evaluated the infectious etiology of placental inflammation in HIV-positive patients. We examined a cohort of placentas from 73 HIV-positive and 41 HIV-negative patients to gain a better understanding of the spectrum of placental inflammatory lesions. Bacterial and viral immunohistochemistry (IHC) was run on a subset of placentas (12 HIV-positive and 7 HIV-negative) with the greatest amount of inflammation. Although few histologic differences were seen between the HIV-positive and HIV-negative groups, chorioamnionitis was of a higher stage in the HIV-positive placentas. An infectious agent was found by IHC in 3 of 7 HIV-negative patients (2 Neisseria spp. and 1 group B Streptococcus ). One HIV-positive placenta showed gram-positive cocci on fetal membranes; organisms were not detected by IHC. In 2 patients, the etiologic agent was not suspected prior to IHC. This study identified that acute inflammation is less common in placentas from HIV-positive patients, compared with HIV-negative patients. However, when severe inflammation is present, infectious organisms may be identified by IHC, providing a more specific diagnosis and offering a beneficial impact in maternal and fetal management.