An investigation of the effect of transplanted renal allografts on human blood mononuclear leucocytes has revealed a significant increase in the rate of ribonucleic acid (RNA) synthesis in peripheral blood mononuclear cells during clinically diagnosed rejection episodes. This increased metabolic activity was shown to be related to a simultaneous increase in the number of “atypical mononuclear cells” present in the circulating blood at this time. These cells are morphologically distinct from lymphoid cells and resemble immature cells of the myeloid series. The appearance of these cells during rejection episodes suggests that they are associated with the immune reaction, rather than with a nonspecific event, and that they are of value for the early diagnosis of rejection episodes in clinical renal transplantation.