Serum uric acid (UA), the final product of purine degradation, has been proposed to be a marker for impaired oxidative metabolism and a possible predictor of mortality in patients with chronic heart failure. To elucidate whether serum UA correlates with the severity and the mortality of primary pulmonary hypertension (PPH), serum UA was assessed in 90 patients with PPH together with other clinical variables. Right heart catheterization was performed in all patients. Serum UA was significantly elevated in patients with PPH compared with age-matched control subjects (7.5 +/- 2.5 versus 4.9 +/- 1.2 mg/ml, p < 0.001). Serum UA negatively correlated with cardiac output (r = -0.52, p < 0.001) and positively correlated with total pulmonary resistance (r = 0.57, p < 0.001). Serum UA significantly decreased from 7.1 +/- 1.9 to 5.9 +/- 1.6 mg/dl with vasodilator therapy, associated with a reduction in total pulmonary resistance from 22 +/- 6 to 17 +/- 7 Wood units. During a mean follow-up period of 31 mo, 53 patients died of cardiopulmonary causes. Among noninvasive variables, serum UA was independently related to mortality by a multivariate Cox proportional-hazards analysis. The Kaplan-Meier survival curves according to the median value of serum UA demonstrated that patients with high serum UA had a significantly higher mortality rate than did those with low serum UA (log-rank test, p < 0.01). These results suggest that serum UA increases in proportion to the clinical severity of PPH and has independent association with long-term mortality of patients with PPH.