Outbreaks of coxsackievirus B5 (CB5) infections occur primarily during peak epidemic years, with comparatively few cases occurring during intervening years. This pattern of periodic CB5 epidemicity is quite distinct from the general endemicity typical of other group B coxsackieviruses. Todetermine the genetic relationships among CBS isolates from different outbreaks, we compared viral RNAs by ribonuclease T1 oligonucleotide fingerprinting. Isolates obtained within an epidemic year had very similar fingerprints, an observation indicating that they were closely related variants of a single genotype. CBS isolates from the major 1972 epidemic were not closely related to the genotype associated with the preceding epidemic of 1967. However, isolates from the most recent CBS epidemic year, 1983, had fingerprints nearly identical to those of the 1967 strains. These findings provide clear evidence for epidemic reemergence of the 1967 genotype and suggest that the virus was maintained under conditions approaching evolutionary stasis during the intervening 16-year period.