BACKGROUND: Guanosine 3':5'-cyclic monophosphate (cGMP) is the second messenger of nitric oxide and atrial natriuretic factor, and mediates local vasodilatation. These vasodilatory factors are important in blood pressure regulation and possibly in the etiology of hypertension. Urinary cGMP levels among normotensive young adults have not previously been studied. SUBJECTS: A subset of normotensive participants from the CARDIA study (n = 563), aged 23-35 years, was studied. The sample was approximately balanced for sex and race (black/white). METHODS: Twenty-four-hour urinary cGMP levels were measured using an enzyme immunoassay; levels were adjusted for creatinine excretion. The blood pressure, smoking status, and risk factors for hypertension [including a family history of hypertension (FHH), the body mass index, education, alcohol intake, and sodium excretion] were also measured. RESULTS: Women excreted more cGMP than did men, and blacks excreted more cGMP than did whites (both P < 0.0001). Excretion of cGMP was also greater among smokers (P < 0.001) and those with an FHH (P = 0.05), and was related directly and independently to sodium excretion (P < 0.02). The diastolic blood pressure (DBP) was related inversely to the excretion of cGMP among individuals without an FHH (r = -0.36, P < 0.001), but not among individuals with an FHH. In multiple regression analysis, the excretion of cGMP remained related significantly to the DBP and accounted for more variance in DBP than did any other variable among those without an FHH (delta R2 = 0.08, P < 0.001). CONCLUSIONS: Urinary cGMP excretion is related inversely and independently to the DBP among those without an FHH but not among those with an FHH, suggesting that cGMP-related vasodilatation is impaired in those with an FHH. Sex differences in urinary excretion of cGMP are consistent with results from studies showing that estrogen increases the endothelial production of nitric oxide.