Twenty-two adult patients with osteomyelitis due to Pseudomonas aeruginosa were enrolled in an open, prospective cooperative study to determine the efficacy of oral ciprofloxacin therapy in a dosage of 750 mg twice a day. Twenty patients received a complete course of treatment and could be assessed for efficacy. There were 12 men and 8 women, with a mean age of 55 years. Six patients had undergone previous, unsuccessful attempts at therapy. Eight patients had clinically important underlying conditions. The most common sites of infection were the sternum (six patients), hip (four patients), vertebrae (four patients), and tibia (two patients). Initial surgical debridement was performed in 18 of the 20 assessable patients. The mean duration of treatment was 2.85 months (range, 1 to 4 months), and that of the follow-up was 27 months (range, 6 to 52 months). Cure was achieved in 19 of the 20 (95%) patients. The only significant adverse effect (which prompted discontinuation of therapy) was severe nausea in one case. Oral ciprofloxacin coupled with adequate debridement is an effective, convenient, and safe therapy in patients with acute and subacute P. aeruginosa osteomyelitis.