We undertook this study to determine the occurrence of rhabdomyolysis in the hyperosmolal state. We reviewed 130 hospital admissions due to diabetic ketoacidosis or hyperosmolal coma, or both. Thirty-one patients (12 men and 19 women) were found to be in the hyperosmolal state. Sixteen of 31 patients showed biochemical evidence of rhabdomyolysis. The clinical and biochemical features of the patients with rhabdomyolysis (Group I) and the patients without rhabdomyolysis (Group II) were compared. Patients in Group I showed a 100-fold increase (7,156 +/- 2,820 IU/L) in serum creatine phosphokinase (CPK) when compared to the patients in Group II (61 +/- 11 IU/L). The mean serum osmolality was much higher (p less than 0.001) in patients with rhabdomyolysis (381 +/- 12 mOsm/kg) than in those without rhabdomyolysis (324 +/- 4 mOsm/kg). The serum sodium level was elevated (p less than 0.001) in Group I patients (151 +/- 4 mEq/L) but not in Group II patients (133 +/- 2 mEq/L). There was a linear association between serum CPK versus serum sodium (r = 0.62, p less than 0.05) and serum CPK versus serum osmolality (r = 0.05, p less than 0.05). The mean serum potassium level was lower (p less than 0.01) in Group I than in Group II. Only two patients (12%) in Group I and almost half the patients (seven of 15) in Group II were hyperkalemic. The mean serum phosphorus level was lower in Group II than in Group I. Four patients in Group I and one patient in Group II developed acute renal failure. Subclinical rhabdomyolysis is a common finding in the hyperosmolal state. Absence of hyperkalemia in the presence of muscle injury, hyperosmolality, hyperglycemia, and acidosis suggested pre-existing total-body potassium deficiency in many of these patients. In addition to hypokalemia, the hyperosmolal state predisposes to the development of rhabdomyolysis.