The primary goal of this research is to use cultured animal cells as a model system to elucidate basic genetic processes in the control of metabolism in man. A variety of biochemical mutants affecting carbohydrate, amino acid, pyrimidine and purine metabolism in Chinese hamster cells in culture have been isolated and characterized. The first group of mutants are those resistant to deoxygalactose and deficient in galactokinase activity. The frequency of mutation increased after chemical mutagenesis and the resistant phenotype persisted in the absence of selection. By somatic cell fusion, the resistant phenotype behaved like a recessive trait. Secondly, we have developed a selective method for conditional lethal mutants. Applying this technique, we have isolated mutants of hamster cells either defective in amino acid transport, ts leucyl tRNA synthetase, or resistant to the arginine analogue canavanine. The last group appear to include those with elevated argininosuccinase activity and those with higher intracellular arginine pools. Finally, we have isolated mutants that are resistant to adenine and adenosine. Initial characterization shows that the resistant phenotype is dominant in cell hybrids and that resistance in different mutants may be due to either a reduced level of the purine salvage enzyme hypoxanthine guanine phosphoribosyltransferase or an increased activity of adenosine deaminase.