Each of the genomic sequences of Methanosarcina acetivorans, Methanosarcina mazei, and Methanosarcina thermophila revealed two homologs of mtaA, three homologs of mtaB, and three homologs of mtaC encoding enzymes specific for methanogenesis from methanol. Two-dimensional gel electrophoretic analyses of polypeptides from M. thermophila established that methanol induces the expression of mtaA-1, mtaB-1, mtaB-2, mtaB-3, mtaC-1, mtaC-2, and mtaC-3 whereas mtaB-3 and mtaC-3 are constitutively expressed in acetate-grown cells. The gene product of one of three mttC homologs, encoding trimethylamine-specific methyltransferase I, was detected in methanol- but not acetate-grown M. thermophila. A postulated role for the multiple homologs is discussed.