Background. This study was done to define the seasonality of respiratory syncytial virus (RSV) epidemics in the southeastern United States. Methods. We tested 5,092 fresh nasal aspirates or washings, using the Kallestad Pathfinder enzyme immunoassay (EIA) or the Directigen RSV membrane EIA according to manufacturers' directions. Results. A total of 1,419 (27.9%) respiratory specimens, collected from pediatric patients between May 1993 and December 1996 at two large southeastern medical centers, were positive for RSV antigen by enzyme immunoassay. A persistent RSV epidemic was documented between July 1993 and December 1996. We defined an epidemic as 2 consecutive months in each of which greater than or equal to 10% of the specimens were positive and greater than or equal to 2 positive specimens detected. The highest percentages of positive specimens were detected in December of 1993, 1994, and 1996, to date, and November 1995. Conclusion, On the basis of our findings, we recommend health care workers consider RSV in the differential diagnosis of acute respiratory illness throughout the year in pediatric patients from the southeast United States.