Kaposi's sarcoma (KS), the most frequent malignant neoplasm associated with acquired immunodeficiency syndrome, often involves the oropharynx and larynx. This study evaluated the efficacy of intralesional vinblastine sulfate injection in oropharyngeal and laryngeal KS. Twenty-four human immunodeficiency virus-positive patients with a total of 26 KS lesions were treated with injections of 0.1- or 0.2-mg/mL vinblastine sulfate solution. Subsequent injections were administered at 4- to 5-week intervals if necessary until the lesions resolved or stabilized. Complete regression was achieved in 16 lesions (62%), 20% to 50% reduction in 4 lesions (15%), and less than 20% reduction in 3 lesions (12%). Two lesions (8%) did not respond, and 1 (4%) grew despite the injections. Thirteen patients experienced no adverse effects. Eleven patients reported pain not relieved by acetaminophen; 5 of these 11 also had ulceration secondary to the injection. Both pain and ulceration were self-limiting. We conclude that vinblastine injection is a viable option for treatment of oropharyngeal and laryngeal KS lesions.