This project is designed to produce lines of rats selected for high and low degrees of tolerance to ethanol. Animals inhale ethanol chronically in specially-constructed chambers, and are then tested for functional tolerance to the hypnotic effect of ethanol. Initial studies have confirmed genetic heterogeneity with respect to the development of tolerance in the N:NIH rats that will serve as breeding stock. Animals demonstrating high or low degrees of tolerance will be mated, with precautions taken to minimize inbreeding. At the limit of selection, animals selected for each trait will theoretically contain all alleles associated with that trait, while alleles not associated with the trait will be randomly distributed. Therefore, these animals will be a resource for all researchers interested in the biochemical determinants of alcohol tolerance.