Rotavirus is the major cause of severe diarrhea in children. A recent study of hospitalizations for diarrhea in the United States suggested that the annual rotavirus epidemic may follow a regional sequence from west to east. As part of a program to establish active surveillance of rotavirus prior to the introduction of vaccines, we obtained 5 years of retrospective data on rotavirus detections from 88 centers throughout North America. Analysis of 34,644 detections indicates that the peak of the annual rotavirus epidemic occurs first in Mexico and the Southwest of the United States in late fall, goes systematically across the continent in the winter, and ends in the Northeast United States and the Maritime Provinces of Canada in the spring. When detections are grouped by region, onset of the epidemic follows the same regional sequence as the peak. To our knowledge, this is the only description of a repetitive geographic sequence for the seasonal epidemic activity of a viral agent. Further studies are indicated to determine whether climate, features of the virus itself, or other factors are responsible for this apparently unique pattern. A system of active surveillance can use this pattern to detect natural alterations in the epidemic behavior of rotavirus and to assess the impact of vaccines.