The introduction and the subsequent use of maximum tolerated dose (MTD) or, more correctly, the estimated maximum tolerated dose (EMTD) in chemical carcinogenesis is reviewed. A historical perspective followed by the chronological development of the concept is described and commented on. The justifications and the criticisms of the EMTD are outlined and rebuttals of the criticisms are presented. The extrapolation of estimated risk from animal bioassay to humans is given and the notion of the ideal experiment is elaborated upon briefly. It is concluded that the EMTD is a necessary, crucial method in determining the carcinogenic activity of chemical substances and natural products until a better replacement is found.

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