The specific effect of zinc deficiency on blood glutathione (GSH) concentrations has not been clearly demonstrated, for earlier results could have been due to differences in dietary intake. To clarify this, we determined blood GSH concentrations over a 17-day period in young, mature rats fed a zinc-deficient diet and compared them with pair-fed controls. Glutathione concentrations based on hemoglobin content increased in both groups but a different rates. After 17 days, the GSH levels increased 20% in deficient rats and 29% in control rats (P less than 0.005). The GSH levels in deficient rats were 11% lower than in controls by 10 days (P less than 0.025) and remained significantly lower thereafter. These results indicate that the decrease in blood GSH levels was a specific result of zinc deficiency.