Acetylation and methylation of erythroid histones was investigated in two patients with pernicious anemia before and after treatment with vitamin B12 in vivo. It was found that vitamin B12 facilitated both acetylation and methylation of histones. Electrophoresis of amino acids obtained from histone hydrolysates prior to treatment with vitamin B12 demonstrated that lysine was present as I-lysine. After treatment with vitamin B12, most of the lysine appeared as methyl-I-lysine. Whether this biochemical lesion is specific for vitamin B12 deficiency or also occurs in folic acid deficiency awaits future studies.