Ethanol induced changes in the brain protein and RNA metabolism have been determined in chronic, physically dependent, and ethanol withdrawn rats. Additionally, chronic ethanol effects were investigated on the (3H) colchicine binding properties of microtubular protein in neuroblastomas grown in culture. Data showed decreased in vitro protein synthetic ability of ribosomes from the cerebral hemispheres and cerebellar brain regions under these conditions. While the sucrose gradient A260 ribosomal profile analysis revealed distinct differences between the physically dependent and withdrawn groups, the tRNA aminoacylation was reduced only in the chronic animals where ethanol seemed to specifically affect the multiple species of leucyl-tRNA. Studies on RNA metabolism showed enzymatic activities for in vitro (3H) ATP incorporation into a polynucleotide fraction by the nuclear soluble and particulate fraction in the ethanol group. Sucrose gradient analysis of these nuclear subfractions revealed many distinct A260 absorbance peaks. The nature of these peaks are now being studied. Other studies revealed high in vitro amino acid incorporation activity by reconstituted ER-ribosome complex. Chronic ethanol exposure to IMR32 human neuroblastomas also resulted in the increased binding of (3H) colchicine to the microtubular protein. In depth experiments in progress wwll determine ethanol's effects on the reaction of protein in whole brain tissue and specific neural cells.