The primary prevention of specific human cancers must take into account the likelihood that most cancers result from a complex interaction between multiple environmental (exogenous) and host (endogenous) factors. In addition, the carcinogenic process often proceeds via multiple steps, including initiation, promotion, and progression. Therefore, assays are required that detect not only initiating carcinogens, but also tumor promoters, hormones, and various cofactors. The known biologic and biochemical properties of initiating carcinogens are reviewed and contrasted with those of tumor promoters. The implications of these differences with respect to the detection and assay of these agents are stressed.