Monitoring mule deer (Odocoileus hemionus) on a former plutonium production site along the Columbia River at the Hanford Site, Washington (USA) revealed 27 (23%) of 116 adult males had unusually shaped, velvet-covered antlers and abnormally developed testicles. We captured 32 males to examine age-class differences and the ratio of affected to unaffected deer and determine whether affected testicles were atrophic or hypoplastic. We found testicular atrophy in most deer with velvet-covered antlers, primarily in animals older than 5 yr. Deer had marked to extreme stages of testicular atrophy, indicating permanent sterility. Decreased serum levels of testosterone and compensatory increased levels of luteinizing hormone and follicle stimulating hormone were detected in all affected males; thus, the gondopituitary hormonal pathway may have responded to abnormally low levels of testosterone in the affected animals. Brucella spp. antibodies in sera were not detected and 9 (90%) of 10 affected animals were seropositive for epizootic hemorrhagic disease virus (EHDV-2) and bluetongue virus (BTV-11) as compared to 12 (63%) of 19 unaffected animals; however, signs of other infectious diseases were not observed. Testicular degeneration generally exceeded that observed with nutritional disorders and poisons in domestic species. Also, severity of the atrophy and apparent lack of other affected tissues suggested that radiation may not be responsible. Testicular atrophy in mule deer has been reported elsewhere; however, neither prevalence has been as high nor or occurrence as well confined to a specific geographical area, as that observed at the Hanford Site. Furthermore, no physiological or age-related influences were described. Documenting the status of such variables and examining their relationships to this phenomenon is a crucial step in understanding the reproductive capacity of a wild deer population.