The relationship of red blood cell (RBC) Na/Li countertransport to the renal handling of lithium and uric acid was investigated in a sample of 176 untreated men. Subjects in the upper quintile of the Na/Li countertransport distribution (n = 40), compared to those in the two lower quintiles (n = 72), had higher serum uric acid levels (0.34 +/- 0.06 v 0.29 +/- 0.05 mmol/L, P less than 0.001) and systolic blood pressure (131 +/- 19 v 123 +/- 16 mm Hg, P less than 0.02) and slightly lower fractional excretion of uric acid (7.5 +/- 1.5 v 8.4 +/- 2.6%, P less than 0.08). The lithium fractional excretion was not significantly related to either blood pressure or RBC Na/Li countertransport. The altered uric acid metabolism in individuals with high RBC Na/Li countertransport could be the expression of an abnormality of renal tubular function.