During the past decade development of selection procedures for isolating a large variety of altered stable phenotypes in mammalian cell culture has been extremely rapid. The list now includes temperature sensitive, auxotrophic, drug resistant and lectin resistant cell lines, as well as cultures containing altered products of differentiation. As a general class, the drug resistant mutants have been studied more often than any of the others because of the wide variety of very interesting and specifically altered mutants that can be isolated, and the ease with which they can usually be obtained. In this review we discuss the essential features of the best studied drug and lectin resistant systems. Also a section on gene transfer has been included since the new technology being developed in this area is certain to have great influence on our understanding of fundamental aspects of somatic cell variation.