Glyburide, a second-generation sulfonylurea hypoglycemic agent, is metabolized by the P-450 hepatic enzyme system. Ciprofloxacin, a widely used quinolone antibiotic, is a recognized P-450 enzyme inhibitor. Conflicting data exist in the medical literature on the ability of quinolone antibiotics to inhibit glyburide hepatic metabolism. We present a case of hypoglycemia and an elevated serum glyburide level after 1 week of ciprofloxacin use in a patient receiving long-term glyburide therapy. Clinicians should consider this potential interaction in patients taking glyburide who require antibiotic therapy.