Based primarily on a single case study, it has been suggested that nonsteroidal anti inflammatory drugs (NSAIDs) may impair cellular potassium uptake, and that this effect may contribute to NSAID-induced hyperkalemia. To explore this possibility, we studied rats that had been pretreated with indomethacin or normal saline and subsequently bilaterally nephrectomized and potassium loaded. There were no significant dfferences between the indomethacin and control groups in the baseline, final, or increment in plasma potassium concentration after a potassium load. Similar results were obtained whether potassium was given intraperitoneally (IP) or intravenously (IV). Serum indomethacin levels confirmed that indomethacin was well absorbed transperitoneally. We conclude that in nephrectomized but otherwise healthy rats, high-dose indomethacin does not impair the cellular uptake of an acute potassium load.