Thirty patients were treated for colonization or for skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus. Three treatment regimens were evaluated, each progressively more aggressive. Our regimen was 750 mg of ciprofloxacin twice daily for 5 days, the second regimen was 750 mg of ciprofloxacin twice daily for 10 to 14 days, and the final regimen was 750 mg of ciprofloxacin twice daily plus 300 mg of rifampin twice daily for 21 days. It appears that ciprofloxacin alone produced an initial eradication rate in at least one site in 50% of the patients, regardless of whether the treatment was for 5 or up to 14 days. All of the patients with eradication became recolonized within 1 week posttherapy. When rifampin was combined with ciprofloxacin, the eradication rate was 100% when the isolates were susceptible to both agents, and these patients remained free of methicillin-resistant S. aureus at 1-week and 1-month follow-ups.