Mutants that require histidine due to an altered structural gene for the histidyl-transfer ribonucleic acid synthetase (hisS) have been isolated by a general selection for histidine-requiring strains in which the mutation producing histidine auxotrophy is unlinked to the histidine operon. One of the mutants has been shown to require an abnormally high internal histidine pool for growth owing to an altered synthetase that is unstable at low histidine concentrations. It is difficult to determine accurately the K(m) for histidine of the synthetase enzyme from the mutant because of the instability of the enzyme at limiting histidine concentrations; however, a histidine K(m) value has been estimated that is approximately 100 times higher than the histidine K(m) of the wild-type enzyme. For the mutant strains to achieve the high internal pool of histidine required for growth, all the systems that transport histidine from the growth medium must be functioning to capacity. Amino acids that interfere with histidine transport strongly inhibit the growth of the mutants. The mutants have been useful in providing a selective genetic marker for transductional mapping in the hisS region. The mutants are discussed as representative of a general class of curable mutants that have an altered enzyme with poor affinity for a substrate or coenzyme.