Chronic dietary administration of pyridoxine HCl (300 mg/kg/day), L-tryptophan (1.26 g/kg/day), or a combination of the two can attenuate the elevation of systolic blood pressure in DOCA-salt-treated rats. With these treatments, the characteristic increase in the weight of the heart accompanying chronic administration of DOCA (786 micrograms/kg/day) was also attenuated. Thus, both tryptophan and pyridoxine possess antihypertensive properties, and the combination of the two appeared to provide greater protection than either alone. The results are consistent with the possibility that pyridoxine, an important cofactor in the metabolic pathways for tryptophan, may facilitate the conversion of tryptophan to antihypertensive compounds. Additional studies will be required to determine which of the metabolites of tryptophan possess antihypertensive properties. Pyridoxal phosphate, one of the metabolites of pyridoxine, was also administered chronically in the diet (1.0 and 2.0% by weight) to rats whose blood pressures were elevated by administration of DOCA. The results of this study suggest that pyridoxal phosphate can also lower the blood pressure of rats with established hypertension. Thus, these studies reveal that pyridoxine, pyridoxal phosphate and tryptophan are potential antihypertensive agents.