Serum methionine and valine have been assayed microbiologically in 31 patients anaesthetized with and in 13 controls anaesthetized without nitrous oxide. Isoleucine has been similarly assayed in five cases and three controls. The preinduction levels of both methionine and valine were considerably below those of semifasting healthy adults. Serum methionine fell significantly in both groups as did valine and isoleucine in the controls. These findings are attributed to dietary restriction before and during the operation. Serum valine was significantly elevated in patients anaesthetized with nitrous oxide but only in those anaesthetized for 3 h or longer. Isoleucine also was elevated in two of the five cases exposed to nitrous oxide. Reasons are given for attributing these elevated levels to the direct action of nitrous oxide. Valine is entirely and isoleucine is partly catabolized along the adenosylcobalamin dependent propionyl-CoA-succinyl-CoA pathway. It is concluded that their elevated levels are caused by the inactivation of adenosylcobalamin by nitrous oxide thereby inducing the methylmalonyl mutase block in this pathway. It is suggested also that the relief of this block by adenosylcobalamin in pernicious anaemia could provide a possible metabolic basis for the well recognized early subjective improvement encountered in this disease following vitamin B12 therapy.