Out of 169 patients with Streptococcal tonsillitis treated with phenoxymethylpenicillin, 13 (8%) developed a new clinical infection with the same streptococcal strain within 2 weeks of completing the therapy (clinical treatment failure) and 24 (14%) were clinically healthy but harboured the same streptococcal strain after treatment (bacterial treatment failure). Patients with clinical treatment failure showed beta-lactamase activity in their saliva pellet significantly more often than patients with bacterial treatment failure, healed streptococcal tonsillitis or non-streptococcal tonsillitis as well as healthy controls. In an interference study, clinical treatment failures were compared with healthy streptococcal carriers, i.e. persons living in the same household and harbouring the same beta-streptococcal strain. 11/12 healthy carriers had alpha-streptococci with interfering activity against their own beta-streptococcal strain, while the corresponding figure for the clinical treatment failures was 2/13. Furthermore, 6/12 healthy carriers had beta-streptococci inhibiting their own alpha-strains, while the streptococci in 11/13 clinical treatment failures had this ability. The beta-lactamase activity and the interference between alpha- and beta-streptococci may be a contributory cause to treatment failure in streptococcal tonsillitis.