Serum samples from 66 recipients of first cadaver donor renal transplants were screened for cytotoxic antibodies to normal T and B lymphocytes and B lymphocytes from chronic lympho-cytic leukaemia patients. In addition, the sera of 44 patients were tested with the B lymphocytes of their respective donors. Donor-specific antibodies were found in 10 of 16 (63%) recipients who had lost their transplant within 2 months, and in 17 of 28 (61%) patients with functioning transplants at 2 months.No correlation was found between the development of B lymphocyte antibodies (either against the panel or the donor) and the onset of an acute rejection episode. In the 17 patients with a successful transplant and donor-specific antibodies, six (35%) had not experienced a rejection episode and another seven patients developed their antibodies after the appearance of the first rejection episode.Thus, our results show that the appearance of donor-specific B lymphocyte antibodies after transplantation is not indicative of graft failure or predictive of acute rejection episodes. However, the common occurrence of such antibodies raises questions concerning the nature of the antigenic stimulus, the specificity of the antibodies, and their role (if any) in transplantation.