Guanosine triphosphate (GTP)-binding proteins are involved, directly or indirectly, in virtually every aspect of cellular growth control and metabolism. At least three major classes of GTP-binding protein have been identified. The first includes elongation factors and initiation factors that are part of the machinery of protein synthesis, and also part of the regulation of this process. The second includes heterotrimeric proteins, referred to as G-proteins, that are involved in transducing signals from external factors to internal second messengers. The third is a large assortment of low-molecular-weight GTP-binding proteins that includes Ras p21 proteins and their relatives. The functions of these small GTP-binding proteins (smgs) are not well understood, but include processes fundamental to normal cell control. The roles of heterotrimeric G-proteins in cell proliferation have been inferred from biochemical studies showing their involvement in production of second messengers (inositol phosphates, cyclic nucleotides, and others) and from the effects of cholera toxin and pertussis toxin on cellular physiology. These effects have been the subjects of several excellent recent reviews (for example, Gilman, Annu Rev Bimbem 1987,56:615-649). In this review, I will focus on GTP-binding proteins whose roles in cell growth control have been deduced from experiments involving manipulation of their genes. This approach (‘reverse genetics’) has the advantage of defining events that are causally related to cell growth, but suffers the limtation that these events are not easily described at the biochemical or mechanistic level. A complete description of the roles of these proteins in cellular proliferation will probably require a combination of genetic and biochemical approaches.