Hypokalemia and paralysis may be due to a short-term shift of potassium into cells in hypokalemic periodic paralysis (HPP) or due to a large deficit of potassium in non-HPP. Failure to make a distinction between HPP and non-HPP may lead to improper management. Therefore, we evaluated the diagnostic value of spot urine tests in patients with hypokalemia and paralysis during 3 years. Before therapy, the urine potassium concentration, potassium-creatinine ratio, and transtubular potassium concentration gradient were determined in a second voided urine sample. Forty-three patients with hypokalemia and paralysis were identified: 30 had HPP and 13 had non-HPP. There was no significant difference in the plasma potassium or bicarbonate concentrations and in the pH of arterial blood between the 2 groups. All but 2 patients in the non-HPP group had urine potassium concentration values less than 20 mmol/L. Although the potassium concentration was significantly lower in the HPP group, there was some overlap. In contrast, the transtubular potassium concentration gradient and potassium-creatinine ratio differentiated patients with HPP vs non-HPP. Although only a mean +/- SD of 63 +/- 36 mmol of potassium chloride was administered in the patients with HPP, rebound hyperkalemia (>5 mmol/L) occurred in 19 (63%) of these 30 patients. Calculating the transtubular potassium concentration gradient and potassium-creatinine ratio provided a simple and reliable test to distinguish HPP from non-HPP. Minimal potassium chloride supplementation should be given to avoid rebound hyperkalemia in patients with HPP.