The bacteria isolated on aerobic and anaerobic culture were compared in 80 unilateral ulcers in patients with homozygous sickle cell (SS) disease, 62 superficial skin lesions, and in 30 diabetic ulcers. In SS disease, the bacterial flora was predominantly aerobic and polymicrobial with Staphylococcus aureus, Pseudomonas aeruginosa and beta-haemolytic streptococci being the major isolates. Repeat sampling of 26 ulcers over a period of 23 weeks indicated the persistence of these three organisms, either singly or in combination in 21 ulcers. Although a variety of Enterobacteriaceae were recovered no single genus predominated and these organisms did not normally persist on follow-up. Simultaneous swabs from bilateral ulcers revealed similar if not identical flora in most cases, indicating good predictive value of a single swab in patients with multiple ulcers. Corynebacterium diphtheriae was recovered from eight ulcers and four of these strains were toxigenic. By contrast, the superficial skin lesions grew mainly S. aureus and beta 6-haemolytic streptococci, and the diabetic ulcers yielded a mixed growth of streptococci, Enterobacteriaceae and anaerobes. The recovery of known skin pathogens from most sickle cell leg ulcers, the persistence of these organisms, and the presence of associated lymphadenopathy, indicates that infection may be a significant factor in the pathology of these lesions.