39 children with prolonged nasopharyngeal carriage (48-328 days) of intermediately to highly penicillin-resistant pneumococci (PRP) were treated for 7 days with rifampicin in combination with amoxicillin (n = 18) erythromycin (n = 17) or clindamycin (n = 4), according to resistance pattern. In all children, except for 1 carrying a rifampicin-resistant strain, control cultures from the nasopharynx 1-2 weeks after the last antibiotic dosage, yielded no growth of PRP. In 2 brothers, PRP with the same serogroup and resistance pattern were found in nasopharynx 10 weeks after the antibiotic treatment. These preliminary findings indicate that antibiotic regimens including rifampicin are effective in eradicating nasopharyngeal carriage, but reappearance of the same strain may occur after several weeks. Such treatments should be given with caution due to the risk of selecting rifampicin-resistant strains. Further controlled studies are needed to determine the optimal combination of antibiotics and appropriate duration of therapy.