H-Ras, K-Ras and N-Ras represent the prototype members of a family of small G proteins that are frequently activated to an oncogenic state in a wide variety of human tumors. Activation is due to point mutations at either position 12 or 61 within their coding sequence. Such mutations cause these proteins to be constitutively converted to their active, rather than the inactive, GDP-bound state. The related human R-Ras gene was initially cloned by low stringency hybridization methods. The R-Ras protein has been shown to interact with the Bcl-2 gene product involved in a signaling pathway that intervenes with apoptosis. Positions 38 and 87 (analogous to positions 12 and 61 in H-Ras) mutants of R-Ras have been shown to be capable of activating oncogenic function. Data has been obtained indicating that R-Ras may exert its biological effect by means of modulating the activity of the Raf-1 kinase on its direct downstream effectors.