Antigenic analysis using monoclonal antibodies and genomic analysis using ribonuclease protection was done on 47 isolates of group A respiratory syncytial virus (RSV) recovered from children in St. Louis during four RSV seasons. Antigenic analysis identified four subgroups; of the three that included more than one member, those designated A/2 and A/2V had characteristic ribonuclease protection patterns. A third subgroup, A/4, exhibited more extensive genomic heterogeneity, but all isolates were distinguishable from those in subgroups A/2 and A/2V. Individual RSV epidemic seasons included isolates representing multiple subgroups of group A and multiple intrasubgroup variants, in addition to isolates from group B. Isolates that were indistinguishable by either antigenic or genomic analysis were present in more than one epidemic season. The subgroups may represent parallel evolutionary lineages, whose relevance to RSV immunity and pathogenesis requires further study.