SUMMARY It is now established that the sensitive radioimmune assays for alpha-fetoprotein and human chorionic gonadotropin are of substantial benefit in the management of patients with testicular tumors. • They can aid in the differential diagnosis of scrotal masses, but only if the levels are elevated. Negative values do not obviate surgical exploration. • They are a superior, though not infallible, method of staging prior to lymphadenectomy in patients with nonseminomatous germ cell tumors. • They are probably indispensible for following nonseminomatous germ cell tumors in Stage I or Stage II disease after initial therapy, and in assessing the effects of ongoing therapy in Stage III disease. • They may be helpful in predicting which patients with seminomas will not respond to conventional therapy. There are, of course, many aspects of the clinical applicability of these markers that are as- yet ill defined. For example, the exact frequency of false negatives in both preoperative evaluations and in patients with Stage III nonseminomatous germ cell tumors remains to be determined. Moreover, we do not know the prognostic implications of negative serum markers in the presence of viable nonseminomatous germ cell tumors. Also, as these assays become more readily available, the chemotherapist and radiation therapist must define the exact role that these markers will have in monitoring and influencing therapy. Is it possible that serial alpha-fetoprotein and human chorionic gonadotropin serum level determinations will allow the chemotherapist to titrate the dosage of chemotherapeutic agents effectively or to predict the response to these agents by first administering challenge doses? Will the radiotherapist decide whether and how to treat a patient with seminoma on the basis of human chorionic gonadotropin levels? These questions require that all physicians treating patients with testicular tumors use reliable and sensitive assays, measure alpha-fetoprotein and human chorionic gonadotropin levels frequently, and report their findings. Finally, clinical studies using these markers have stimulated interest in other aspects of testicular tumors that promise additional clinical benefit. For example, histochemical staining for alpha-fetoprotein and human chorionic gonadotropin of tissues obtained from testicular tumors may alter the pathologic classification of these neoplasms. As discussed by Dr. Jewett in another part of this symposium, marker studies in animal models have helped to advance our understanding of the cellular origins of germ cell tumors. Lastly, in vitro and in vivo laboratory experiments have demonstrated the feasibility and possible clinical applicability of using anti-alpha-fetoprotein and anti-human chorionic gonadotropin antibodies for diagnosis and as a new form of therapy.19.24