We evaluated the safety and efficacy of ofloxacin administered both by the intravenous route and orally in 26 men with serious skin and soft tissue infection. Twenty-one patients completed antimicrobial therapy and were fully evaluable. Of these, 18 were judged to be cured, while 3 failed therapy either during or within 2 weeks after completion of therapy. Overall, Staphylococcus aureus was the most commonly isolated pathogen and was found to be susceptible to ofloxacin in 12 of 14 patients. Two patients, 1 with a tolerant isolate of S. aureus, the other patient with a resistant isolate of S. aureus, responded clinically to ofloxacin therapy; a third patient with an initially ofloxacin-sensitive isolate failed therapy, and on subsequent culture an ofloxacin-resistant S. aureus was isolated. Ofloxacin was well tolerated and efficacious in the treatment of skin and soft tissue infections including those caused by staphylococci and streptococci.