Fifty patients with cellulitis were evaluated prospectively using cultures of aspirates from the advancing edge of cellulitis, skin biopsy specimens, and blood. Potential microbial pathogens were isolated in 13 patients. Biopsy specimen cultures were positive in ten patients, while aspirate and blood cultures were positive in five and two, respectively. Aspirate, biopsy, or blood cultures were more often positive in patients with apparent primary lesions than in patients without such lesions. Apparent primary sites of infection were identified and cultured in 24 patients. β-Hemolytic streptococci were isolated from 17 primary lesions, and coagulase-positive staphylococci were present in 13. Both organisms were isolated from ten primary lesions. Among patients with positive aspirate, biopsy, and/or blood cultures, the same pathogens were also isolated from primary sites in ten of ten patients. Clinical features, including temperature, white blood cell count, and erythrocyte sedimentation rate, were not predictive of positive aspirate, biopsy, or blood cultures. These cultures provided no microbiologic information that was not obtainable from culture of primary lesions. © 1986, American Medical Association. All rights reserved.