Although infections are a significant cause of mortality and long-term morbidity of newborns, the early diagnosis of neonatal infections remains difficult. It has been shown recently that up-regulation of CD45RO expression on umbilical cord lymphocytes might be a good indicator for intrauterine viral infections. To evaluate clinical relevance of changes in CD45 isoforms to the diagnosis of neonatal infections, we examined CD45RA and CD45RO expression on total, CD4+, and CD8+ lymphocytes from newborns. Lymphocytes from 55 newborns who were hospitalized in Kiyose Metropolitan Children's Hospital or Yamanashi Medical University Hospital were analyzed. Newborns were classified into three groups according to the possibility of bacterial or viral infection; I ("no" infection, n = 24), II ("possible" infection, n = 17), and III ("definite" infection, n = 14). Results were compared between two of three groups. The CD45RO expression on total or CD4+ lymphocytes in group III (bacterial 12, viral 2) was significantly higher than that in group I or II. Particularly, the CD45RO expression on CD4+ lymphocytes was always greater than 10% in group III, and showed no overlap with the respective value in group I. After termination of infection, the increased CD45RO expression in group III gradually returned to normal levels. These results indicate that not only viral but also bacterial infections trigger transient and reversible changes in CD45 isoform expression by neonatal CD4+ T lymphocytes. This may be a novel marker for the early diagnosis of neonatal infections.