During a 2-yr study of carcinogenesis by CdCl2 in male Wistar [Crl:(WI)BR] rats, weekly clinical observations during the last 6 mo of the study revealed many cases of persistent tumor-like masses at the site of the metal identification tags in the ears of the animals. A total of 14 tumors (mostly compound osteosarcomas) was diagnosed in 168 rats. Histologically, almost 90% of the rats in this study (henceforth referred to as Study I) showed some significant lesion at the tag site including various degrees of chronic inflammation, chondrous hyperplasia, and osseous metaplasia of the pinnal cartilage. In marked contrast, only two tumors were detected in 193 animals in a second study (Study II) in the same strain of rats, and only 56% of the rats had lesions at the tag site. A high incidence (>25%) of clinically severe inflammation at the tag site was seen early in Study I and persisted during the first 6 mo of the study, while the incidence of such reactions in Study II was never more than 1%. Elemental analysis of the tags provided no explanation for the differences between the two studies, as tags used in both studies were of the same composition, predominantly nickel and copper. Metallic internal prostheses have induced local malignancies in humans and animals, and the present observations provide further evidence of the hazard posed by such devices at the site of prolonged contact with tissues. These findings suggest that a persistent tissue reaction may be an important factor in tumor development.