Administered in supraphysiologic doses, the hormone melatonin may reduce blood pressure, particularly nocturnal blood pressure. However, whether lower physiologic levels of melatonin are an independent risk factor for the development of hypertension has never been reported. We examined the association between first morning urine melatonin levels and the risk of developing hypertension among 554 young women without baseline hypertension who were followed for 8 years. Cox proportional hazards models were adjusted for age, BMI, physical activity, alcohol intake, smoking status, urinary creatinine, and family history of hypertension. During 8 years of follow-up, a total of 125 women developed hypertension. The relative risk for incident hypertension among women in the highest quartile of urinary melatonin (>27.0 ng/mg creatinine) as compared with the lowest quartile (<10.1 ng/mg creatinine) was 0.49 (95% confidence interval 0.28-0.85, P < 0.001). First morning melatonin levels are independently and inversely associated with incident hypertension; low melatonin production may be a pathophysiologic factor in the development of hypertension.