Doxycycline has been considered a safe broad-spectrum antibiotic for patients with renal failure. Although doxycycline possesses many of the metabolic properties of the tetracycline group, toxic blood levels usually do not occur because of the drug's unique extrarenal route of excretion. We report here a patient with stable chronic renal failure whose renal function acutely and reversibly deteriorated coincident with a 14-day course of doxycycline. Review of the literature suggests that occasional patients may have impairment of the nonrenal excretory pathway for doxycycline. We speculate that these patients are at risk for developing nephrotoxic levels of this antibiotic.