Most patients with acute cellulitis due to Streptococcus pyogenes have a striking onset of high fever and systemic toxicity. Even if hospitalization is deemed necessary for initial treatment, most patients respond promptly to appropriate antibiotic therapy and can be managed as outpatients for most of the treatment regimen. Described is a 48-year-old, previously healthy woman with acute cellulitis and lymphadenitis who did not initially respond to treatment despite proved in vitro activity against the patient's S. pyogenes isolate. The strain grew as a mucoid colony phenotype on blood agar plates. The mucoid characteristic of the strain may have accounted for the patient's lack of response to initial therapy, and previously published clinical and laboratory data support this impression.