The disposition by rats of tritium-labeled doxycycline was investigated. More drug is eliminated from the circulatory system by diffusion into the lumen of the small intestine than by excretion with urine or bile. Enzymatic degradation of drug either does not take place at all, or to a small extent only. These results help explain the clinical observation that doxycycline unlike other tetracyclines does not accumulate in patients with renal insufficiency. Doxycycline passes relatively easily through the intestinal wall and is less dependent upon normal renal function for its elimination than other tetracyclines of lesser lipophilicity.