Rheumatic fever is a disorder with a presumed post-streptococcal autoimmune etiology. The streptococcal pathogenesis of rheumatic fever is supported by studies that have demonstrated the effectiveness of penicillin prophylaxis in preventing recurrences of this illness. A trial of penicillin prophylaxis in the PANDAS subgroup demonstrated that penicillin was not superior to placebo as prophylaxis against GABHS infections in these children, but this outcome was felt to be secondary to non-compliance with treatment, and there was no decrease in the number of neuropsychiatric symptom exacerbations in this group. In a study comparing azithromycin and penicillin, both drugs were completely effective in preventing streptococcal infections - there were no documented titer elevations during the year-long study period for children taking either penicillin or azithromycin. Comparable reductions in the severity of tics and obsessive-compulsive symptoms were also observed. Thus, penicillin was not performing as an "active placebo" as originally postulated, but rather provided effective prophylaxis against Group A beta-hemolytic streptococcal. Both azithromycin and penicillin appear to be effective in eliminating GABHS infections, and reducing neuropsychiatric symptom severity; thus, between-group differences are negligible. Since increasing the "n" to demonstrate superiority of one prophylactic agent over another would be impractical, we have amended the study design to address two issues: