SUMMARY: Marked elevation ol' histidine decarboxylase activity of allografts during rejection and prolongation of allograft survival with inhibitors of this enzyme prompted study of the effect of enzyme inhibitors on antibody production. The most effective inhibitors, the α-hydrazino analogue of histidine alone and the combination of semicarbazide and a pyridoxine-deficient diet, significantly inhibited antibody formation. Semicarbazide plus a pyridoxine-deficient diet produced marked inhibition of antibody formation to salmonella flagellar antigen in rats. Insignificant inhibition resulted following 66 and 102 days of pyridoxine- deficient diet alone. In the standard. Jerne agar plaque assay in mice, semicarbazide plus pyridoxine-deficient diet and the α-hydrazino analogue of histidine alone and in combination with a pyridoxine-deficient diet produced inhibition of antibody formation (19 S)and reduction in spleen size. The capacity of remaining lymphoid cells to produce antibody also was diminished. No such changes accompanied the use of semicarbazide alone and pyridoxine-deficient diet alone. When semicarbazide plus pyridoxine-deficient diet was initiated after antigen administration in the Dresser-Wortis modification of the Jerne assay, marked reduction in antibody production (7 S) and spleen size were found. No change was produced by pyridoxine-deficient diet alone.