The effect of methylmercury (MM) on protein synthesis was examined with respect to nutritional deficiency due to decreased food intake, method of amino acid administration, and amino acid uptake. Female rats were administered orally 40 mg MM hydroxide/kg and were compared with both ad libitum and pair‐fed control groups. Synthesis of blood, liver, kidney, and cerebellar proteins of pair‐fed controls was significantly lower than for ad libitum‐fed controls. Relative to ad libitum‐fed controls, MM transiently increased synthesis of blood proteins and then decreased it for blood and liver proteins. In contrast, using pair‐fed controls, MM increased synthesis of blood and liver proteins. Comparison with either control showed MM to increase protein synthesis in the kidney and decrease it in the cerebellum. Intra‐peritoneal and intravenous administration of the [14C] amino acids showed similar results. The action of MM on protein synthesis seemed independent of its action on amino acid uptake, since MM did not affect aminoisobutyric acid uptake in the liver and cerebellum and decreased it in the kidney. In summary, we found that the effect of MM on food intake plays a significant role in the action of MM on protein synthesis and must be accounted for with pair‐fed controls.