In the twenty years since the first unequivocal reports (including inheritance data) on the selection of mutants in vitro [ !, 2], a large number of mutants have been isolated, and reviews have frequently updated the progress, most extensively in a recent treatise [3]. The earliest reports made no use of deliberate mutagenesis, relying instead on the wide genetic variation exhibited by cultured cells, based on spontaneous mutation rates and possibly enhanced by genetic instabilities of rapidly dividing cells in culture [ 4]. The fact that the numbers worked in favour of selection of spontaneous mutants, when a dominant monogenic trait with a strong positive selection pressure was involved, probably delayed a critical evaluation of the role of chemical and physical mutagens in enhancing "mutation frequency". This was exacerbated by difficulties in reliable quantification of the latter term, given that single cell cultures were generally not in use, and colony forming potential (or plating efficiency) was usually profoundly influenced by viable cell density.