By varying the composition of the growth medium and the genotype of the bacterial strain, five isoenzymes of CoA-dependent aldehyde dehydrogenase could be detected in Escherichia coli. Two isoenzymes (A, mol. wt 520 000; and B, mol. wt 370 000) were produced only in the presence of ethanolamine and vitamin (or coenzyme) B12 ('inducible isoenzymes'), whereas the other three isoenzymes (C, mol. wt 900 0000; D, mol. wt 120 000; and E, mol. wt 720 000) were produced only in the absence of ethanolamine and vitamin B12 ('repressible isoenzymes'). Partial purification and characterization of these isoenzymes revealed strong similarities, with respect to pH optima and substrate affinities, between isoenzymes within either of the two classes, but significant differences between the two classes. Mutant studies demonstrated that the relationships between the isoenzymes and between CoA-dependent aldehyde dehydrogenase and ethanolamine ammonia-lyase are both structural and regulatory in nature, and a two-operon model is proposed to account for the common control of the enzymes of ethanolamine catabolism in E. coli.