Following the introduction of effective antiviral chemotherapy, rapid antigen assays have been utilized increasingly, instead of cell cultures, for detection of the respiratory syncytial virus from lower respiratory tract specimens. Because antigen assays, unlike cell culture, cannot amplify low levels of the virus to a detectable level, assay sensitivity is especially dependent on high-quality specimens. In addition, the assays are unable to detect other viruses or bacteria with which the patient may be infected. This review summarizes results from clinical studies of the performance of cell cultures and the more commonly used antigen assays, describes factors that may lead to false-positive or false-negative test results, and makes recommendations for the selection of procedures for the reliable detection of microbial pathogens from patients suspected of being infected with respiratory syncytial virus.