Expansion of activated T cells expressing the T-cell receptor (TCR) γ/δ, CD45RO, and HLA-DR antigens is a prominent feature of acute infection with Ehrlichia chaffeensis in humans. The fate of these activated cells and the resolution of the γ/δ T-cell response with return to the usual α/β T-cell populations in this disease are not clearly understood. At a morphologic level, apoptotic cells are present in the peripheral blood during the acute and resolution phases of the infection. Simple culture of density gradient-separated lymphocytes from the blood of patients with acute ehrlichiosis produced cell death rapidly in the media compared to α/β T cells. This loss of viability after incubation was apparently mediated by apoptosis, based on flow cytometric and morphologic analyses. The results suggest that most primed (CD45RO⁺) and activated (HLA-DR⁺) γ/δ T cells in acute ehrlichiosis might be subject to removal from the body by programmed or apoptotic cell death.