Human CD4+ Th1 and Th2 clones were infected with human T-lymphotropic virus type I (HTLV-I) and followed up for a 12 month period in culture. PCR analysis showed that proviral DNA and viral mRNA were present in both Th1 and Th2 infected clones, throughout the entire culture period. Thus, HTLV-I exhibited neither preferential tropism nor exerted differential immortalizing activity in Th1 versus Th2 cells. All the infected clones immediately lost their antigen dependency for growth and continuously proliferated in IL-2-conditioned medium without need for additional stimulation. Infected Th1 and Th2 clones equally showed high expression of CD25, HLA-DR, CD44, CD30 and CD45RO. Infection with HTLV-I altered the cytokine profile in Th1 and Th2 clones. Both types of clones produced IL-6 and TNF-alpha. Th1 infected clones retained their ability to secrete IFN-gamma, but lost IL-2 gene expression. Th2 infected clones lost IL-4 gene expression, retained the ability to produce small amounts of IL-5 and acquired IFN-gamma expression.