Previous studies have revealed that the expression of CD38 on CD8+ T cells is a strong predictor of disease progression in human immunodeficiency virus (HIV)-infected individuals. Those studies were performed using fresh patient samples over an extended trial period. After demonstrating the validity of assay results on cryopreserved cells, we performed a retrospective study using frozen cell samples to determine the predictive value of CD38 expression in patients with CD4 counts above 400 cells/microl. The CD38 expression as measured by antibody binding capacity and the CD38 median channel were shown to be associated with time to new opportunistic infection or death (both P < 0.001). These results suggest that CD38 expression on CD8+ T cells, whether fresh or frozen, provides a useful predictor of HIV disease progression.