Dysfunction of the nitric oxide (NO) system is potentially involved in the development of hypertension, but only limited data are currently available from experimental or clinical studies. We investigated cross-sectionally the relation between urinary excretion of cyclic guanosine 3',5'-monophosphate (cyclic GMP), a second messenger of NO, and hypertension in a general population sample of Japanese men and women. The samples comprised 1541 subjects (788 men and 753 women) aged 40-79 years who participated in cardiovascular risk surveys between 1997 and 2002 and underwent a 24h urine collection. Urinary excretion of cyclic GMP was measured using a 125I-labeled cyclic GMP radioimmunoassay, and was adjusted for urinary creatinine excretion (nmol/mmol creatinine). Urinary cyclic GMP excretion was 66.0+/-62.0nmol/mmol creatinine (mean+/-S.D.). Compared with normal blood pressure individuals, the multivariate-adjusted mean value of urinary cyclic GMP excretion was significantly higher in people with moderate hypertension, but not higher in severe hypertension. Among subjects with hypertensive end-organ damage, we observed reduced urinary cyclic GMP excretion in severe hypertension and no increased excretion in moderate hypertension, compared with normal blood pressure. Although we had the limited number of subjects with severe hypertension (n=15), our data suggest that NO bioactivity may be increase in the early stage of hypertension but decreased in severe hypertension with end-organ damage.