Volatile anesthetics are indispensable for modern medical practice. Despite more than 150 years of determined investigation, the sites and mechanisms of action of these clinically essential drugs remain unknown. We are using molecular genetic studies in the model eukaryote Saccharomyces cerevisiae (yeast) to investigate the cellular activities of these compounds. We find that volatile anesthetics inhibit yeast growth and that there are striking parallels between the activity of these compounds as yeast growth inhibitors and as mammalian anesthetics. These parallels include: rapid and reversible effects; very sharp dose-response curve; direct correlation between potency and lipophilicity; mixtures of different anesthetics are additive in their effects; and lipophilic compounds that are nonanesthetic in mammals do not affect yeast. These similarities suggest that identification of targets or mechanisms of action of volatile anesthetics in yeast will provide insight into the activity of these drugs in mammals. Molecular genetic analysis of yeast with altered anesthetic sensitivity indicates that starvation for specific amino acids plays a key role in anesthetic response. This starvation response leads to inhibition of initiation of translation and growth arrest. Similar effects on protein synthesis occur in mammalian tissue. Our present studies involve characterizing 1) the specific targets of the anesthetics and 2) the pathways involved in the translational arrest in yeast.