Benzathine penicillin G (BPG) is effective for secondary prophylaxis of rheumatic fever (RF). However, interval between injections a remains a controversial matter. In a study population of 74 patients, following the initial diagnosis of RF, 3-weekly BPG (1.2 million units) regimen was started. During the first three-week period, serum penicillin concentrations were examined on the 7th, 14th and 21st days and throat culture done for group-A b hemolytic streptococcal (GABHS) infection. Ten patients (13.5%) at 21st day of injection had low serum penicillin concentration after the first BPG. GABHS was isolated in 5 patients during this period. Although two of these 5 patients had symptoms of respiratory tract infection, according to laboratory data, the other three were accepted as carriers. All 74 patients were then followed-up for rheumatic recurrence (RR) during long-term period (6 to 60 months, mean 25 +/- 5 months). There was no RR among regular (missing no more than one injection a year) group. We concluded that 3-weekly BPG regimen was satisfactory for secondary prophylaxis in RF, even though serum penicillin level was inadequate during the third week in some of the patients.