The persistence and proliferation rate of mouse skin papillomas were studied in HA/ICR mice initiated with 7,12-dimethylbenz(a)anthracene and promoted three times weekly with phorbol myristate acetate. When the promoter treatments were stopped, rapid (half-time, 24 days) and slow (half-time, greater than 140 days) components of papilloma regression were observed. When the promoter dose was increased, the major effect was an increase among the rapidly regressing papillomas. Increases in the epidermal pulse-labeling index and the number of dermal inflammatory cells produced by phorbol myristate acetate in normal skin were reversible when the phorbol myristate acetate was stopped, but high pulse-labeling index values in papillomas were not reversible. Antithymocyte serum had no effect on regression, although ethylphenylpropriolate, a nonpromoting irritant, slowed the regression sufficiently to increase the half-time from 24 to 57 days. The action of the promoter in overcoming the regression tendency of the papillomas may explain certain features of the role of nonspecific irritation and the importance of promotion frequency in determining tumor yield.