In the treatment of group A streptococcal tonsillitis, as the bacteria are located on the epithelial surface, an important determinant of outcome is the concentration of penicillin in extracellular tonsillar surface fluid. Accordingly, we investigated the concentration of penicillin in serum, and penetration to tonsillar surface fluid and saliva in nine patients with acute group A streptococcal tonsillitis and in nine healthy controls. Among the healthy subjects, despite high serum penicillin concentrations (mean, 2.04 micrograms/ml), there was no penetration to tonsillar surface fluid or to saliva, whereas erythromycin penetrated to tonsillar surface fluid in 3/6 cases. Of the nine patients with acute tonsillitis, on the first day of treatment eight manifested high concentrations of penicillin in tonsillar surface fluid (mean, 0.34 micrograms/ml--i.e. well above the minimal inhibitory concentration (MIC) for group A streptococci), but penetration to saliva was found in only two patients. On the tenth day of treatment, penicillin was not present in the saliva of any of the patients and was present in the tonsillar surface fluid of only one. The results suggest that measurable concentrations of penicillin in tonsillar surface fluid can only be obtained in the presence of inflammation with fluid exudation through the tonsillar epithelium.