A 64-year-old man undergoing major head and neck surgery received clindamycin for perioperative antimicrobial prophylaxis. On the third postoperative day, he became acutely neutropenic. The neutropenia resolved 3 days later, after the administration of filgrastim. After ruling out other causes of acute neutropenia, we determined that the neutropenia was secondary to clindamycin toxicity. While clindamycin-induced neutropenia has been reported elsewhere, to our knowledge this is the first report of its occurrence following head and neck surgery. Otolaryngologists should be aware of this potentially serious reaction.