OBJECTIVE High-dose trimethoprim-sulfamethoxazole (TMP-SMX) is known to cause hyperkalemia by blocking amiloride-sensitive sodium (Na) channels in distal nephrons. The purpose of this study was to establish whether the standard dose of TMP-SMX could cause electrolyte disorders. METHODS Serum Na, potassium (K) and creatinine (Cr) levels were examined retrospectively in 53 of 77 patients prescribed TMP-SMX, before and after taking the antibiotic combination. RESULTS Electrolyte disorders (Na < 135 mEq/l and/or K > 5.0 mEq/l) were found in 14 of the 53 patients (26.4%) during TMP-SMX treatment. The average dose was 145.7 +/- 24.9 mg/day. The dose of TMP was significantly larger in patients with electrolyte disorders (267.7 +/- 84.2 mg vs. 101.9 +/- 9.38 mg, p = 0.0024). Electrolyte disorders were also seen in 9.1% and 22.2% of patients given the low dose (TMP < 80 mg) or standard dose (TMP 80-120 mg) of TMP-SMX, respectively. Electrolyte disorders were seen in 85.7% of patients with renal dysfunction (Cr > 1.2 mg/dl), compared with 17.5% of patients with normal renal function (p = 0.0008). Logistic regression analysis showed that the dose of TMP and the presence of renal dysfunction increased the incidence of electrolyte disorders with an odds ratio of 2.35 and 80.29, respectively. CONCLUSIONS Electrolyte disorders, particularly hyperkalemia and hyponatremia can be detected in patients given TMP-SMX. These disorders are more frequent in patients given high doses, but can also be detected after low-dose administration. Renal dysfunction accelerates the incidence of electrolyte disorders induced by TMP-SMX.