BACKGROUND: Zinc supplementation may be beneficial for health. Assessing exchangeable zinc pools may be a useful approach to evaluate zinc status. OBJECTIVE: We evaluated the effects of long-term supplementation with 2 moderate doses of zinc on the mass of exchangeable zinc pools. DESIGN: Three groups of healthy, late-middle-aged men (n = 16 per group) participated in a stable-isotope zinc kinetic study after 6 mo of daily supplementation with 0 (placebo), 15, or 30 mg Zn. At the end of the supplementation period, each subject received an intravenous injection of 0.89 mg (70)Zn, and the plasma zinc disappearance curve was monitored for the next 10 d. Two approaches were used to determine the characteristics of the exchangeable zinc pools: 1) formal 3-compartmental modeling and 2) a simplified determination of the total mass of the rapidly exchangeable zinc pool (EZP). RESULTS: In the placebo group, the exchangeable zinc pool masses for the 3 considered pools were as follows: 2.15, 12.7, and 100.5 mg Zn. The rapidly exchangeable zinc pool mass in the placebo group was 143 mg Zn. Zinc supplementation significantly increased the exchangeable zinc pool masses regardless of the approach used to determine these pools. In addition, these data confirm that exchangeable zinc pool masses correlate positively with total zinc intake and negatively with subject age and do not correlate with plasma zinc concentrations. CONCLUSION: Our data show that long-term supplementation with 2 moderate doses of zinc is an efficient way to increase exchangeable zinc pool masses in late-middle-aged men.