Nephrotoxicity of allopurinol is enhanced in experimental hypertension. Hyperuricemia is present in 20-40% of pediatric and adult patients with essential hypertension. This metabolic abnormality may represent an additional risk factor for the development of cardiovascular disease. Therefore, we performed the following studies to determine 1) whether hyperuricemia is more prevalent in the spontaneously hypertensive rat (SHR) and 2) whether allopurinol treatment has a beneficial effect on the development of hypertension in this strain, based on its capacity to lower the serum uric acid concentration and to act as an antioxidant agent. SHR and control Wistar-Kyoto (WKY) rats were assigned to two groups, one given tap water to drink and the other provided water containing allopurinol (400 mg/l) to furnish an approximate daily dose equal to 100 mg/kg body wt. This treatment was maintained for 15 weeks. The serum uric acid levels were similar in untreated SHR and WKY rats (1.85 +/- 0.10 versus 1.66 +/- 0.14 mg/dl; p = 0.28). In the control WKY rat strain, allopurinol therapy did not adversely affect weight gain or hematocrit and did not cause an increase in mortality. It resulted in a moderate decrement in kidney function (creatinine clearance: allopurinol-treated group 0.32 +/- 0.09 versus control group 0.46 +/- 0.04 ml/min/100 g body wt, in conjunction with mild-to-moderate tubulointerstitial inflammation (allopurinol-treated group 0.9 +/- 0.4 versus control group 0). 