Phorbol derivatives (phorbol-12,13-diacetate, phorbol-12,13-dibenzoate, phorbol-12,13-dibutyrate, and phorbol-12-myristate-13-acetate) interact with cortisol on a molecular basis. These molecular interactions are demonstrated via dexamethasone receptor assays and by changes in spectrophotometric characteristics when equimolar solutions of these phorbol compounds together with cortisol are compared to those of the pure solutions. The phorbol compounds characterized by modifications in the molecular ring structure and by substitution at position C20, lose the capacity to bind cortisol. The tumor promoting effects of phorbol compounds are apparently achieved, in addition to other well-known mechanisms, by neutralizing cortisol, thus suppressing its regulatory effect on cell proliferation.