The multiple in vivo and in vitro tests described thus far in this chapter present the experimental- ist or the regulator with an extensive amount of data from which to draw conclusions about the carcinogenic potential of the test agent. In addition, epidemiological studies (Chapters 11 and 12) provide perhaps the most definitive means of estimating the carcinogenic potential to hu- mans from exposure to a specific agent. While such studies, if definitively positive, are the best evidence for the carcinogenic potential of an agent to the human, the evidence is usually ob- tained after an exposure has occurred in a population. In general, epidemiological studies can detect differences between populations only when there is approximately a twofold increase above the background incidence of neoplasia in the control population. Since many more agents than those classified as group 1 by IARC exhibit carcinogenic potential, the in vitro and in vivo tests described earlier have been used as surrogates in attempting to determine carcinogenic po- tential and risk to the human population. The results of such tests clearly offer qualitative infor- mation regarding the identification of agents exhibiting some potential hazard with respect to one or more aspects of the process of carcinogenesis as we know it today. Major difficulties remain in attempting to extrapolate in a scientific and meaningful way information obtained from in vitro and in vivo tests to an estimation of the potential risk of such agents to the human population as inducers of disease, especially neoplasia. As might be expected, a number of prob- lems are involved in the scientific and practical application of information developed from short- and long-term tests to the estimation of human risk.