Background: Our previous studies suggest that serum γ- glutamyltransferase (GGT) activity may be related to oxidative stress, supporting findings of experimental studies. To further examine the role of GGT in relation to oxidative stress, we investigated the association between serum carotenoids and tocopherols, which have antioxidant properties, and serum GGT. Methods: Study participants were 3128 black and white men and women 17-35 years of age in 1985-1986. Serum carotenoids and tocopherols were measured at years 0 and 7, and serum GGT was measured at years 0 and 10. Results: Circulating concentrations of a-carotene, β-carotene, and β-cryptoxanthin inversely predicted the serum GGT concentration measured 10 years later in a dose-response manner (P for trend <0.01). Year 0 zeaxanthin/lutein was weakly inversely associated with year 10 GGT (P for trend = 0.08), and year 0 lycopene was unrelated to year 10 GGT. Adjusted geometric means of serum GGT at year 10 according to quintile of the sum of four carotenoids at year 0 (a-carotene, β-carotene, β-cryptoxanthin, and zeaxanthin/lutein) were 19.9, 19.4, 18.9, 17.8, and 17.3 U/L (P for trend <0.01). Year 0 α-tocopherol was also a significant inverse predictor of year 10 serum GGT concentration (P for trend = 0.03), whereas γ-tocopherol showed an inconsistent or possibly U-shaped association. However, year 0 serum GGT did not predict serum antioxidants measured 7 years later. Conclusion: Our present findings support the contention that serum GGT concentration is a marker related with oxidative stress.