Immunological studies on scrub typhus (ST) have been limited mostly to animals despite the possible difference in the immune responses among the species of the hosts. To investigate in vivo cellular immune responses to ST in humans, we characterized T-cell subsets in the peripheral blood samples from 30 healthy control subjects (HC), 11 patients with nonrickettsial acute infections (NRAI), and 6 patients with ST by a dual labeling method of flow cytometry. In ST, HLA-DR+CD3+ cells were greatly increased compared with those in HC and NRAI (HC, 2.3 +/- 1.3%; NRAI, 4.5 +/- 4.4%; ST, 32.5 +/- 14.7% values are means +/- SD). CD8+ cells were also significantly increased (HC, 29.5 +/- 5.9%; NRAI, 30.5 +/- 9.4%; ST, 44.9 +/- 11.5%), while CD4+CD45RA+ cells were significantly reduced (HC, 23.6 +/- 8.2%; NRAI, 23.3 +/- 12.3%; ST, 12.9 +/- 7.1%) in ST. The unique changes in the T-cell subsets in the peripheral blood samples from the patients with ST support the importance of the cellular immune responses to the natural infection of ST in humans.