Twenty needle biopsies from 14 patients were taken at times of renal dysfunction, and frozen sections were stained for class I and class II major histocompatibility complex (MHC) antigen expression using the immunoperoxidase technique and monomorphic mouse monoclonal antibodies. Eight of the 9 biopsies taken during periods of dysfunction attributed to cyclosporine toxicity had normal levels of class II expression. In contrast, 9 of the 10 biopsies taken during episodes of rejection had easily recognized increases in class II expression. In the one case where no definite clinical diagnosis was possible, no class II induction was present. Class I levels were less definitive but tended to be markedly raised in the cases of rejection, and only mildly raised in the cases of nephrotoxicity. Biopsy results can be available within 1 1/2-2 hr. The test is therefore likely to be of value in the correct diagnosis of the cause of renal dysfunction and thereby improve the management of cyclosporine-treated renal transplant patients.