Treatment of difficult-to-treat infections such as osteomyelitis or infections related to indwelling medical devices requires lengthy antibiotic therapy and adequate surgical debridement. Teicoplanin, a glycopeptide antibiotic with a long half-life, was used three-times weekly in the treatment of these infections. After a period of daily dosing with teicoplanin, patients were treated with an intravenous dose of 12 mg on mondays, wednesdays and fridays. A control group of patients were treated with teicoplanin daily. Teicoplanin levels were measured during the study. Thirty-six patients were enrolled in the study: 14 with vertebral osteomyelitis, 12 with infected orthopedic implants, 7 with osteomyelitis and 3 with arterial prosthetic infections. The duration of treatment ranged from 60 to 360 days. Cure was obtained in 21 (58%) patients and improvement in 15 (42%) patients. Trough and peak serum concentrations in three-time weekly patients were 16.2+/-7.2 mg/l and 58.7+/-14.4 mg/l. In the control group trough and peak serum concentrations were 18.9+/-13.6 mg/l and 52.2+/-27 mg/l. Adverse events occurred in 6 patients: mainly mild liver toxicity. Three times weekly teicoplanin seems to be a valuable option in the treatment of chronic infections.