The quantitative deep-tissue microbiology of the infected feet of 32 patients with diabetes mellitus was studied, and the clinical features of the patients were analyzed. Techniques of specimen collection designed to avoid contamination from surface flora were used to study amputated lower limbs. Cultures of deep tissue from six patients yielded only aerobes, and for one patient, only anaerobes. Cultures for 25 patients yielded a mixture of aerobes and anaerobes. A mean of 4.81 species (2.84 aerobes and 1.97 anaerobes) were isolated from each patient. The density of growth of anaerobes, however, was significantly higher than that of aerobes. Culture specimens obtained by curettage of the base of the ulcer correlated better with results of deep-tissue culture than did those obtained by needle aspiration or swab of the ulcers. The most frequently isolated organisms were Bacteroides species, anaerobic streptococci, group D streptococci, Clostridium species, and Proteus species. The presence of anaerobes was associated with a higher frequency of fever and foul-smelling lesions and with the presence of a foot ulcer. Prior antibiotic therapy did not appear to influence the nature of the microorganisms isolated. The polymicrobial nature of this disease should be considered when antimicrobial therapy is indicated.