The expression of HLA-DR by T lymphocyte subpopulations recognized by monoclonal antibodies and flow cytometry was monitored in 10 normal controls, 15 patients on hemodialysis, 25 recipients of a renal allograft with stable graft function, 16 transplant recipients suffering rejection episodes, and 4 transplant recipients with cytomegalovirus (CMV)4 infection. No significant differences in HLA-DR expression were observed in the OKT4-reactive subpopulation among these controls and patients. In the 16 patients who suffered rejection episodes a significant increase in HLA-DR expression by OKT8-reactive cells was observed. In the 10 patients in whom rejection episodes occurred later than 1 week after transplantation, the percentage of OKT8-reactive cells that expressed HLA-DR was dramatically increased 2-6 days before the onset of clinical symptoms of rejection (P less than 0.001 Student's t test). When the rejection episode responded to treatment, expression of HLA-DR on the OKT8-reactive cells decreased--whereas in 3 patients who lost their grafts because of irreversible rejection, expression of HLA-DR remained elevated. In addition, the 4 patients with CMV infection had increased percentages of OKT8-reactive cells that expressed HLA-DR (P less than 0.001 Student's t test). This increase in expression of HLA-DR coincided with the onset of clinical symptoms of the CMV infection, and the expression of HLA-DR returned to normal values after the titers of antibodies to CMV had increased significantly and symptoms of infection had disappeared.