Patient expectations and physician attitudes are often cited as factors in the overuse of antibiotics. This study examined whether clinical error might also be important. In treating 517 patients with sore throat, family physicians estimated the probability that group A streptococcus infection was present. Two thirds of antibiotics prescribed were to culture-negative patients and therefore considered unnecessary. Physicians overestimated the probability that a group A streptococcal infection was present by an average 33.2% in these cases, compared with 6.9% otherwise (p < 0.001). The rate of unnecessary prescribing was 5.1% when the physician estimate differed from the true probability of a group A streptococcal infection by <10%, 16.0% for an error of 10-29%, 35.6% for an error of 30-49%, and 78.3% when the chance of the infection was overestimated by 50% or more. Clinical error in estimating the likelihood of group A streptococcal infection probably contributes to unnecessary antibiotic use in patients with sore throat.