In a prospective study, the cytomegalovirus (CMV) pp65 antigenemia assay was compared with detection of CMV by blood culture in 67 consecutive CMV-seropositive patients undergoing autologous marrow or peripheral blood stem cell transplantation. Antigenemia occurred in 26 patients (38.8%) a median of 33 days (range, 12-74) after transplant. Viremia was detected in 5 patients (7.5%) a median of 30 days (range, 12-74) after transplant and was treated with ganciclovir in 3. Antigenemia occurred sporadically at low levels (< 5 positive cells/slide) in 19 patients (28.4%) and never resulted in CMV disease. Two of 7 patients who presented with or progressed to antigenemia of > 5 positive cells/slide developed fatal CMV pneumonia 8 days later. Neither patient had CMV viremia before onset of pneumonia. Thus, quantitative CMV pp65 antigenemia may be useful in guiding antiviral treatment in seropositive autograft recipients.