The induction of differentiation by inhibitors of nucleotides synthesis was studied in Bacillus subtilis and in yeast. The following major results were obtained: 1) Several biochemical pathways that are normally needed for Bacillus subtilis sporulation are not required when sporulation is induced, in the presence of glucose and ammonia, by decoyinine, an inhibitor of GMP synthetase. This was shown by the use of mutants blocked in the citric acid cycle or gluconeogenesis, or by manganese deficiency which prevents the function of phosphoglycerate mutase. 2) The yeast Saccharomyces cerevisiae can in appropriate purine-free growth media also be induced to undergo meiosis and then to sporulate by the addition of amethopterin (in the presence of thymine) or by mycophenolic acid.