The in vitro study of somatic cell genetics originally made possible a new approach to human genetics, which by passed the need for mating and thus permitted enormous expansion of the genetics of man and other mammals. More recently, by increasing the variety of cell mutants obtainable, by the production of hybrids containing single or small numbers of human chromosomes, by development of the immunogenetics of macromolecules in differentiated cell membranes, and by combining the techniques of somatic cell genetics with those of recombinant DNA, new approaches are available to the problem of regulation of mammalian gene expression. Experiments are presented offering the possibility of application of these techniques to human gene mapping, detection of mutagenic actions, identification of genes involved in differentiation, and a beginning of molecular understanding of the pathology of the aneuploid diseases.