Background: The histopathology of AIDS associated myelopathy (AM) closely res embles that of myelopathies due to cobalamin or folate deficiency, with white ma tter vacuolization in the spinal cord. The pathogenesis of AM appears unrelated to direct HIV infection of the spinal cord. There is abnormal trans methylation metabolism in AM, with decreased availability of the methyl group donor S aden osyl methionine (SAM). The authors hypothesized that treatment with L methioni ne,the direct metabolic precursor of SAM, might improve AM. Objective: To determ ine the safety and efficacy of L methio nine treatment in AM. Methods: Fifty six patients with clinical diagnosis of AM were randomized to a Phase II, double blind, bplaceo controlled study comparing the effect of L methionine 6 g/day in two divided doses with that of placebo. Study duration was 12 weeks. All pat ients had somatosensory evoked potentials with prolonged central conduction time (CCT) at entry. Change in CCT was the primary endpoint of the study. Frequency of adverse events (AEs) was used to a ssess safety. Secondary endpoints were strength, spasticity, and urinary functio n. Biochemical measurements included serum methionine and homocysteine and CSF S AM. Results: There were no significant differences in AEs between the two groups . Serum homocysteine increased in L methionine treated patients from 7.2 (±5. 2 SD) to 12.6 (±6.15 SD) μmol/L. The mean CCT at baseline was 25.9 millisecond s (±7.3 SD) for the treatment group and 24.1 milliseconds (±7.0 SD) for the pl acebo group. At completion, it was 3.0 milliseconds (±6.1 SD) for the treatment group and 23.6 milliseconds (±5.5 SD) for the placebo group (p = 0.17). In a s ubset of 15 patients with CSF studies, SAM levels increased in the L methionine but not in the placebo group (p = 0.07). There was no significant effect of tre atment on strength, spasticity, or urinary function. Conclusions: L Methionine was safe and well tolerated although in some patients induced an increase of ser um homocysteine. There was a nonsignificant improvement in CCT in treated patien ts but no benefit in any of the clinical measures. Background: The histopathology of AIDS associated myelopathy (AM) closely res embles that of myelopathies due to cobalamin or folate deficiency, with white ma tter vacuolization in the spinal cord. The pathogenesis of AM appears unrelated to direct HIV infection of the spinal cord. There is abnormal trans methylation metabolism in AM, with decreased availability of the methyl group donor S adenosyl methionine (SAM). The authors hypothesized that treatment with L methioni ne, the direct metabolic precursor of SAM, might improve AM. Objective: To determ ine the safety and efficacy of L methio nine treatment in AM. Methods: Fifty six patients with clinical diagnosis of AM were randomized to a Phase II, double blind, bplaceo controlled study comparing the effect of L methionine 6 g / day in two divided doses with that of placebo. Study duration was 12 weeks. All pat ients had somatosensory evoked potentials with prolonged central conduction time (CCT) at entry. Change in CCT was the primary endpoint of the study. Frequency of adverse events (AEs) was used to a ssess safety. Secondary endpoints were strength, spasticity, and urinary functio n. Biochemical measurements included serum methionine and homocysteine ​​and CSF S AM. Results: There were no significant differences Serum homocysteine ​​increased in L methionine treated patients from 7.2 (± 5. 2 SD) to 12.6 (± 6.15 SD) μmol / L. The mean CCT at baseline was 25.9 milliseconds (± 7.3 SD) for the treatment group and 24.1 milliseconds (± 7.0 SD) for the pl acebo group. At completion, it was 3.0 milliseconds (± 6.1 SD) for the treatment group and 23.6 milliseconds (± 5.5 SD) for the placebo group (p = 0.17) With as ubset of 15 patients with CSF studies, SAM levels increased in the L methionine but not in the placebo group (p = 0.07). There was no significant effect of tre atment on strength, spasticity, or urinary function. Conclusions: L Methionine was safe and well tolerated though in some patients caused an increase of ser um homocysteine. There was a nonsignificant improvement in CCT in treated patien ts but no benefit in any of the clinical measures.