The pathogenesis of AIDS-associated vacuolar myelopathy (VM) may be related to abnormality of transmethylation mechanisms in the nervous system. To evaluate the safety and potential efficacy of the methyl-group donor L-methionine in AIDS-associated VM, we conducted a pilot clinical trial in 12 patients with VM. Seven of the nine patients who completed the study had clinical and electrophysiologic improvement. Controlled studies may be indicated to assess the efficacy and safety of L-methionine in AIDS-associated VM.