To determine antibiotic requirements in patients with renal insufficiency, the rate of disappearance of sodium methicillin and sodium oxacillin from the blood of patients with negligible renal function was measured. Both antibiotics persisted longer than in normals, and the serum disappearance curves were not appreciably influenced by hemodialysis, indicating that extrarenal mechanisms were more important than removal through the hemodialyzer. Surprisingly, oxacillin disappeared from the serum more quickly than methicillin despite being much more highly bound to serum proteins. This may be due to more rapid destruction or excretion of oxacillin by the liver. Recommendations are made for dosages of these two antibiotics in uremic patients.