The bioassays, now known as the short-term tests, were introduced into the armamentarium of the toxicologist initially to identify those chemicals that interacted in some way with DNA, and thus had a presumption of potential carcinogenicity. These tests were escalated into high visibility almost single handedly by Ames, who provided a rapid and inexpensive test to detect agents that could induce gene mutations in a set of special strains originally derived from the bacterium Salmonella. The tests have reached their adolescence with many of the uncertainties and confusions that accompany that age, along with the opportunity for analysis and reflection to determine how best to use the valuable resource. Several attempts have been presented recently to deal with the issue of the qualitative and quantitative relationships among the short-term tests and their end-points in vivo. The genotoxicity tests have provided a rich data source that needs some creative and courageous analysis.