BACKGROUND Hyponatremia is commonly observed following transurethral resection of the prostate or endometrial resection when the operative field is irrigated with hypotonic glycine. Although glycine-induced hyponatremia has been associated with brain damage, the mortality is low, and it has been suggested that the condition might not be hypo-osmolar and thus might not cause brain edema. OBJECTIVE To determine if glycine-induced hyponatremia is a hypo-osmolar condition. METHODS The study was a retrospective evaluation of 13 men who underwent transurethral resection of the prostate and 5 women who underwent transcervical endometrial resection at 2 university medical centers. In all patients, hypotonic glycine (200 mmol/L) was the irrigating solution. Measurements were made of the plasma sodium, osmolality, glucose, urea, glycine, and ammonia; and arterial pH, PO2 and PCO2. Mortality and the occurrence of respiratory arrest were recorded. Data are given as mean (+/- SE). RESULTS The plasma sodium in 18 patients was 106 +/- 2 mmol/L and the measured osmolality was 235 +/- 5 mOsm/kg H2O. Glycine was measured as the difference between measured and calculated plasma osmolality and was 18 +/- 2 mmol/L. Four patients suffered respiratory arrest; all died. One patient had elevated blood ammonia (130 mumol/L) with a plasma sodium level of 110 mmol/L. She was treated with endotracheal intubation and respiratory support plus hypertonic sodium chloride, and recovered. The other 14 surviving patients were treated with hypertonic sodium chloride. CONCLUSIONS Patients who undergo transurethral resection of the prostate or endometrial resection with hypotonic glycine as the irrigating medium can experience symptomatic hyponatremia that is hypo-osmolar and can be fatal. Therapy with hypertonic sodium chloride was associated with survival in 14 of 14 patients. Ammonia intoxication also can develop, and can be managed with respiratory support.