Using the double-nested reverse transcription-polymerase chain reaction, we assayed human T-cell leukemia virus type I (HTLV-I) tax/rex-encoded mRNA in the peripheral blood mononuclear cells (PBMCs) of asymptomatic carriers as an index of the expression of HTLV-I in vivo in relation to the proviral DNA level. HTLV-I tax/rex mRNA was detected in only 1 (3.3%) of 30 samples with medium or lower proviral DNA levels, but it was detected in 11 (39.3%) of 28 samples with high HTLV-I proviral DNA levels, estimated as equal to or more than the proviral DNA of 10 ng of HUT102 (i.e., HUT102 cells were used as positive controls). The mean number of interleukin-2 receptor alpha (IL-2R alpha)-positive cells as a percentage of the total number of PBMCs was higher (13.2%) in the tax/rex mRNA-positive carriers with high proviral DNA levels than in the carriers who were mRNA negative (8.4%) (p = 0.004, Wilcoxon test). These results suggest that virus activation as indicated by the presence of tax/rex mRNA in asymptomatic carriers with high proviral DNA levels is associated with an elevation of the IL-2R alpha-positive cells in vivo.