Respiratory syncytial virus (RSV) has been reported to cause severe morbidity and mortality among cancer patients receiving chemotherapy with or without autologous peripheral blood stem cell transplantation (APBSCT). However, little is known about the natural history of this infection in these patients, and current standard practice, aerosolized ribavirin plus intravenous immunoglobulin (IVIG), is extremely expensive, difficult to use, and not supported by controlled clinical trials. The purpose of this observational study was to determine the frequency, seasonality, morbidity, and mortality of RSV infection in a group of cancer patients receiving cytotoxic chemotherapy with neither ribavirin nor IVIG treatment. During the period of October 3, 1997, through October 14, 1998, 190 cancer patients (median age, 58 years; 71 women) underwent viral nasopharyngeal washing prior to chemotherapy. Multiple myeloma (MM) accounted for most patients (147, 77%). RSV was recovered from cultures taken from 71 patients (37%) throughout the year, although more frequently during fall and winter seasons (P <.001) than spring and summer. Serious respiratory complications developed in 19 (27%) of 71 RSV-positive patients versus 24 (20%) of 119 patients whose RSV cultures were negative (P =.384). The presence of renal failure or increased lactate dehydrogenase (LDH) prior to chemotherapy and the development of mucositis were the only predictive factors for severe respiratory complications. Recovery of RSV from nasopharyngeal washings among cancer patients is common, occurs throughout the year, and does not appear to increase serious morbidity or mortality. RSV infection may not necessarily be a contraindication for APBSCT or an indication for therapy with aerosolized ribavirin and IVIG.