Two cases of severe myeloneuropathy and macrocytic anemia associated with a low serum level of vitamin B12 after prolonged exposure to nitrous oxide are reported. In both cases, the neurological manifestations worsened initially despite B12 supplementation, although in one case the use of methionine seemed to arrest the progression of the disease and accelerate recovery. This offers further support for the biochemical hypothesis of methionine synthetase inhibition by nitrous oxide and reproduces in man previously reported animal studies with methionine. Methionine may be an important first-line therapy in the initial treatment of neuropathy and myeloneuropathy induced by nitrous oxide, and has a hypothetical role in the treatment of subacute combined degeneration of the cord.