Objectives: Sustained hyperkalaemia usually indicates a defect in renal potassium (K+) excretion and can be due to severe impairment of glomerular filtration rate (GFR). The major determinants of renal K+ secretion were studied in hyperkalaemic and normokalaemic elderly subjects to probe the major determinants of hyperkalaemia in this setting. Design: The transtubular potassium gradient (TTKG) provides an index of tubular K secretion and normally rises in patients with significant hyperkalaemia. Both GFR(glomerular filtration rate) and TTKG were assessed at baseline and repeated after 3 hours following ingestion of 0.1mg of fludrocortisone in three groups. Setting: An acute general hospital in the West of Ireland. Participants: 23 subjects in total; 8 older patients with unexplained hyperkalaemia (OHK), 8 older patients with normokalaemia (ONK) and 9 young normokalaemic controls (YNK). Measurements: The GFR was either measured by 24 hour creatinine clearance estimation or calculated using the Cockroft and Gault formula. TTKG was calculated using a specific formula. Results: Mean baseline TTKG was similar in all three groups and consequently inappropriately low in hyperkalaemic subjects. Three hours post fludrocortisone, the TTKG had risen significantly from baseline levels in the young subjects only (from 7.5+/-0.09 to 11.6+/-1.1, p<0.05). No significant increase was noted in either older group at this timepoint. Conclusions: The inappropriately low baseline TTKG in the OHK group as well as the absence of a response to fludrocortisone indicate tubular insensitivity to aldosterone. GFR values in both OHK (40.06+/-2.31) and ONK (55.58+/-6.1) groups were significantly lower than those in the YNK group (101.66+/-6.9). In aggregate, these findings indicate that older hyperkalaemic patients typically have both impairment of glomerular filtration and renal tubular K+ secretion and highlights the requirement for vigilance in elderly patients when using medications which interfere with tubular function.