Geranylgeranyl transferase I (GGTase I), which modifies proteins containing the sequence Cys-Ali-Ali-Leu (Ali: aliphatic) at their C-termini, is indispensable for growth in the budding yeast Saccharomyces cerevisiae. We report here that GGTase I is no longer essential when Rho1p and Cdc42p are simultaneously overproduced. The lethality of a GGTase I deletion is most efficiently suppressed by provision of both Rho1p and Cdc42p with altered C-terminal sequences (Cys-Ali-Ali-Met) corresponding to the C-termini of substrates of farnesyl transferase (FTase). Under these circumstances, the FTase, normally not essential for growth of yeast, becomes essential.