The lymphocyte transformation test (LTT) was used to elucidate whether certain side effects induced by radiographic contrast media have an immunologic etiology. Groups studied were: 8 patients who had previously experienced adverse reactions in association with urography, 6 patients who underwent urography without notable side reactions, 17 occupationally exposed nurses, and 9 unexposed controls. The lymphocytes from 2 hypersensitive patients and from 11 nurses exhibited a positive proliferative response to amidotrizoate. Five nurses who had shown a positive response, had a previous history of hypersensitivity reactions when handling contrast media, whereas the remaining 6 were free of symptoms. Amidotrizoate-specific memory cells were absent in patients who underwent urography without signs of hypersensitivity and in 7/9 of unexposed control subjects. Lymphocytes from patients sensitive to amidotrizoate cross-reacted to structurally related ionic contrast media while non-ionic contrast agents did not induce proliferation of the lymphocytes. Thus, ionic radiographic contrast agents have antigenic properties in man. Irradiated mixtures of radiographic contrast media and serum proteins were, in general, not effective in inducing an LTT response.