The growth arrest-specific gene, Gas-1, was cloned from quiescent NIH3T3 mouse fibroblasts. Gas-1 mRNA accumulates when cells enter quiescence (Go) and expression is down-regulated by stimulation with serum or growth factors. DNA synthesis is inhibited when expression of Gas-1 is forced in normal or transformed NIH3T3 cell. Gas-1 encodes an integral membrane protein with two putative transmembrane domains flanking an extracellular region and with no significant similarities to any known proteins. The presence of an extracellular arginine-glycine-aspartic acid sequence suggests that the Gas-1 protein can associate with integrin-type receptors and may be involved in contact inhibition or in anchorage of the cells to the extracellular matrix. Since expression of Gas-1 is specific to quiescence, the Gas-1 protein may be required to sustain growth arrest or be involved in the control of differentiation. Thus, Gas-1 could act as a tumor suppressor gene by preventing uncontrolled proliferation. The authors report here the localization of GAS1 to human chromosome arm 9q at bands q21.3-q22.