Chemotherapy and radiation therapy are commonly used alone or in combination in the curative management of many malignancies in adolescent and adult males. Over the last 15-20 years, the striking success in the treatment of some common cancers in reproductive males has led to increasing concern for damage to normal tissues, such as the testes, resulting from curative cancer treatment. Indeed, a major future goal for cancer treatment will be to improve on the complication-free cure rate. Inherent in achieving this goal is to understand the pathophysiology and clinical expression of testicular injury. Both chemotherapy and radiation therapy result in germ cell depletion with the development of oligo- to azoospermia and testicular atrophy. The type of drug (particularly the alkylating agents), duration of treatment, intensity of treatment, and drug combination are major variables in determining the extent and duration of testicular injury. Testicular injury with chemotherapy also appears to vary with the age of the patient at the time of treatment. Newer drug combinations are now being used which appear to have curative potential in tumors such as Hodgkin's disease and germ cell testicular cancer with less potential for testicular injury. The most accurate and complete information on radiation injury to the testes is derived from two studies of normal volunteers who received graded single doses directly to the testes. A clear dose-response relationship of clinical and histological testicular damage was found with gradual recovery occurring following doses of up to 600 cGy. While these two studies provide an important clinical data base, radiation therapy used in treating cancers involves multiple daily treatments, usually 25-35 delivered over several weeks. Additionally, direct testicular irradiation is seldom used clinically. Based on several recent studies of testicular injury following conventional radiation therapy, it appears that fractionated scatter irradiation may have a more profound effect than single dose irradiation and that recovery of normal testicular function may be delayed. Testicular injury from doses as low as 20 cGy is reflected principally in transient elevations in serum FSH levels. With higher radiation doses (greater than 200 cGy), Leydig cell dysfunction is also seen as evidenced by elevations in LH. Recently, testicular shields have been constructed which can reduce scatter dose to the testes by up to a factor of 10. Today, the routine use of a testicular shield and other technical innovations in the clinical use of radiation therapy should minimize the risk of significant testicular injury.