Human herpesvirus-6 (HHV-6) is a recently identified T lymphotropic virus. We have examined the ability of HHV-6 to replicate in mature and immature human thymocytes. Infection of both cell populations revealed that only mitogen-activated mature thymocytes could support efficient virus replication. Because interleukin-2 (IL-2) plays a central role in T cell activation we investigated its effect on HHV-6 replication. Unexpectedly, addition of recombinant IL-2 at concentrations exceeding 10 U/ml strongly inhibited the virus-induced cytopathic effect. Electron microscopic examinations and immunofluorescence assays revealed a threefold reduction in the fraction of infected cells, and almost total absence of extracellular virions in the IL-2-treated cultures. It will therefore be of interest to determine whether the IL-2-mediated inhibitory effect plays some role in the establishment of HHV-6 latency in the human host.