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To determine whether a single dose of amoxicillin administered to a symptomatic child with confirmed strep throat might allow the child to return to school as little as 12 hours later.We enrolled 111 evaluable children with sore throat plus a positive streptococcal rapid antigen detection test (RADT) as well as a positive result for group A Streptococci (GAS). After throat swab specimens were obtained, all participants received a single dose of amoxicillin (50 mg/kg). Twelve to 23 hours after the first dose of amoxicillin, all participants returned in the morning of day 2 for a second throat swab specimen. At the day 2 visit, a nurse or medical assistant obtained an interval history, tympanic membrane temperature, and a pediatrician or nurse practitioner examined the oropharynx.On the morning of day 2, only 10 of 111 participants continued to have a positive RADT result, confirmed by overnight throat culture. GAS were not detectable on the day 2 throat specimen by RADT and also by culture in 91% of the study participants (confidence interval: 86–96%). Seven of 10 failures had a marked decrease in number of β-hemolytic colonies, which were 3+ to 4+ on the initial overnight culture plate and decreased to 1+ on the follow-up (obtained on day 2) throat culture plate. Two participants continued to have 3+ or 4+ GAS after incubation of the second throat culture specimen.Even in the late afternoon, a full dose of amoxicillin (50 mg/kg) administered after notification of positive RADT results for GAS resulted in nondetection of GAS in 91% of children the next morning. All children treated with amoxicillin for “strep throat” by 5 PM of day 1 may, if afebrile and improved, attend school on day 2.