The number and morphology of mast cells (MCs) in the duodenal submucosa and the histamine content of blood and isolated peritoneal mast cells were estimated sequentially in male weanling Sprague-Dawley rats magnesium (Mg)-depleted for up to 48 days. Blood histamine levels increased 4--5-fold by 14 days of Mg depletion and subsequently declined to levels similar to those in pair-fed Mg-adequate controls. In the same period, the submucosal MCs continuously increased in number, beginning to plateau at 6--7 times the control number between days 36--48 of Mg deficiency. Massive MC degranulation was seen in the early stages of Mg-depletion but subsided after 16--20 days. Subsequently, the submucosal MCs appeared small and rounded. They showed reduced staining with toluidine blue indicating a deficiency in the mucopolysaccharide component of the storage granules. Histamine content of purified peritoneal MCs from Mg-deficient rats was reduced by 10 days of Mg depletion and remained at or below one-third the control level throughout the depletion period. The data suggest that the MCs remaining or developed during chronic Mg depletion are deficient in their capacity to store and secrete histamine.