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A marked degree of hyperproliferation and hyperplasia of the epidermis secondary to experimentally induced inflammation in the corium was induced in the flank skin of guinea pigs. The substances used to evoke a granulomatous inflammation were beryllium oxide and carrageenan. The epidermal response to this subepidermal process was studied autoradiographically and it was found that the epidermal reaction was similar to that found after direct epidermal trauma such as stripping of the horny layer. It is assumed that dermal factors are responsible for initiating this epidermal reaction and their possible nature is briefly discussed.