We have previously reported the preparation of monoclonal antibodies specific for antigens localized in the rat renal papilla. Three of the monoclonal antibodies reacting with antigens localized in papillary and cortical collecting duct epithelia were selected for the development of enzyme-linked immunosorbent assay (ELISA)-type assays. The papillary antigens ('PapA') determined in these tests were designated PapAl (applying the monoclonal antibody PapX 5C10), PapA2 (applying the monoclonal antibody PapX 12F6), and PapA3 (applying the monoclonal antibody PapXI 3C7). Using these assays antigen excretion was determined in the urine of rats. Depending on the test compound used. the application route, and the dose, the observed antigen release patterns differed. Whereas after a single intraperitoneal application of 2-bromoethanamine or of propyleneimine an increased release of PapA1 but not of the two other antigens was observed oral application of bromoethanamine had minor effects. In contrast, both a single intraperitoneal application or repeated oral applications of indomethacin resulted in an increased release of all the three antigens. Daily application of ipsapirone in the diet or in drinking water resulted in significantly elevated urinary release of PapAl which increased incrementally for the duration of the application. Release of PapA2 and PapA3 was not affected and remained in the normal range. These results show that with the tests developed changes in the rat renal papilla caused by xenobiotics can be detected early by urinary analysis and monitored during follow-up studies. Moreover. the different antigen release patterns obtained after application of the different compounds suggest a possible differing mode of action.