Repetitive topical applications of 2 micrograms TPA twice weekly for 37 to 52 weeks induced a sustained epidermal hyperplasia, hyperplasia of hair follicles, and increased dermal cellularity in SENCAR mice. In addition, after 52 weeks of protracted promoter treatment most animals developed generalized amyloidosis involving liver and spleen, as well as interstitial nephritis. Severe pyelonephritis and papillary necrosis were also frequently seen. Reactive lymphoid hyperplasis was also a frequent finding. Chronic administration of TPA is not an inocuous treatment affecting only the interfollicular epidermis. The general effects of the promoter on the animals, probably through impairment of the immune system, decreased markedly their longevity. (Copyright (c) Environmental Health Perspectives Vol. 68, pp. 75-80, 1986.)