Uric acid transport in renal cortical slices from a selected line of hyperuricemic chickens was investigated. Slices from the hyperuricemic (HUA) line accumulated less than half as much uric acid as slices from a control (LUA) line when uric acid in the medium varied from 0.01 to 5 mM. Uric acid uptake by both lines increased as the uric acid concentration in the medium was raised from 0.1 to 0.5 mM, but was markedly inhibited in the HUA line at 3-5 mM. Omission of sodium or potassium from the incubation medium inhibited uric acid uptake by slices from both lines. Ouabain inhibited uric acid uptake in the LUA line. The sodium and potassium requirements for initiation of uric acid uptake were higher, and the potassium requirement for maximal uptake was lower, for slices of the HUA line. No genetic differences in potassium or sodium contents of slices were observed when the potassium content of the incubation medium was altered or when the medium contained ouabain. These studies indicate that hereditary hyperuricemia in chickens may be due to a qualitative change in renal uric acid transport which involves the interaction of cations in the transport process.