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Purpose: We determined and compared the presence and frequency of interferon-alpha 2b receptors in urothelial neoplasms and normal urothelium, since the biological activity of interferons becomes apparent only after they bind to specific receptors., Materials and Methods: With our method detection of interferon-alpha 2b receptors required a large number of cells, that is more than 1 x 10(6) cells per ml. We studied 14 patients with relatively large tumors of all stages and grades. Three patients had grade I, 4 grade II and 7 grade III disease. As controls we used biopsies of normal urothelium from 14 patients who underwent transvesical prostatectomy. Interferon-alpha 2b receptors were detected quantitatively through the binding of radiolabeled 125iodine human recombinant interferon-alpha 2b in normal and malignant urothelial tissue samples. The interferon-alpha 2b receptors are expressed as receptor sites per cell, and the results were evaluated with Scatchard analysis., Results: The number of interferon-alpha 2b receptor sites per cell ranged from 43 to 100 (mean plus or minus standard deviation 62 +/- 18) in normal urothelium and from 110 to 210 (mean 174 +/- 25) in malignant epithelium. This difference was statistically significant (p < 0.001), Student's t test 13.75). The difference in the number of interferon-alpha 2b receptors in grades I plus II and grade III tumors is suggestive but not statistically significant (p < 0.10, Student's t test 2.075). High grade tumors expressed greater numbers of interferon-alpha 2b receptors than low grade tumors., Conclusions: The method used needs refining so that it will require fewer cells to determine interferon-alpha 2b receptors. Interferon-alpha 2b receptors are detected in bladder urothelium and are abundant in malignant tissue with increasing frequency as tumor grade increases. If we can establish, in the future, a correlation of the number of interferon-alpha 2b receptors with the potential response of patients to intravesical instillation therapy with interferon, we might have an important prognostic method for selecting subgroups of patients with transitional cell carcinomas who will benefit from interferon-alpha 2b instillation.