Gamma-glutamyltransferase (GGT), which maintains cellular concentrations of glutathione, may be a marker of oxidative stress, and GGT itself may produce oxidative stress. We performed a prospective study to examine whether serum GGT predicts diabetes and hypertension. Study participants were 4844 black and white men and women 18-30 years of age in 1985-1986; they were reexamined 2, 5, 7, 10, and 15 years later. Year 0 GGT cutpoints were 12, 17, 25, and 36 U/L (overall 25th, 50th, 75th, and 90th percentiles; the laboratory cutpoints for abnormal are 40 U/L in women and 50 U/L in men). We deleted 32 participants with prevalent diabetes and 140 participants with prevalent hypertension from the respective incidence analyses. After adjustment for study center, race, sex, and age in proportional hazards regression, the hazard ratios across year 0 GGT categories were 1.0, 1.6, 1.7, 4.0 (95% confidence interval, 2.0-8.1), and 5.5 (2.7-11.1) for 15-year incident diabetes and 1.0, 1.2, 1.7 (1.2-2.2), 2.3 (1.7-3.2), and 2.3 (1.7-3.2) for hypertension. Additional adjustment for year 0 alcohol consumption, body mass index, cigarette smoking, and physical activity attenuated this relationship, but GGT remained a significant predictor. Serum GGT within a range regarded as physiologically normal is associated with incident diabetes and hypertension. Considering known functionality of GGT, these associations are consistent with a role for oxidative stress in risk for diabetes and hypertension.