A unique case of fatal necrotizing mediastinitis secondary to acute suppurative parotitis is reported. The infection was the result of synergistic necrotizing cellulitis caused by mixed aerobic and anaerobic bacteria. To the best of the authors' knowledge, this is the first reported case of necrotizing mediastinitis resulting from a descending acute suppurative parotitis. Acute parotitis should be included in the broad spectrum of infections resulting from synergism between aerobic and anaerobic bacteria in which anaerobes indigenous to the oral cavity predominate.