To investigate the possible influence of a polymorphism of the Nos3 gene on menarche and onset of menopause in humans. Cohort study.Academic research institution.Ninety-one consecutive Caucasian postmenopausal women. Peripheral venous puncture and a patient questionnaire were administered.A tandem repeat polymorphism in intron 4 of Nos3 was analyzed by polymerase chain reaction amplification. The common B allele was identified on 143 of 182 chromosomes (frequency 0.79). The polymorphic A allele was present on 39 chromosomes (frequency 0.21). The genotype frequencies were as follows: 58.2% (B/B), 40.7% (A/B), and 1.1% (A/A). Age at menarche, number of deliveries, number of miscarriages, and onset of menopause did not differ between genotypes. Smoking and increased body mass index were associated with an earlier onset of natural menopause.In contrast to mouse models, in humans Nos3 does not seem to modulate onset and cessation of menses.