ARHI contains a highly conserved GTP-binding domain, a putative effector domain distinct from that of RAS and RAP proteins, and a C-terminal membrane localization motif. Northern blot analysis detected a 1.9-kb ARHI transcript in all normal breast and ovarian epithelial cell cultures tested, as well as in normal ovary, heart, liver, pancreas, and brain. Expression was absent in nearly all breast and ovarian cancer cell lines and all primary ovarian cancer cell lines tested. Western blot analysis detected a 26-kD ARHI protein in all normal breast and ovarian cell lines but not in any breast and ovarian cancer cell lines tested. Expression of ARHI in breast and ovarian cancer cell lines but not in lung cancer cell lines led to growth inhibition. Stimulation of normal cell lines with growth factors led to decreased expression of ARHI as well as the cell growth inhibition-associated protein WAF1.