Fifteen chronic enteric carriers of Salmonella typhi were treated with amoxicillin trihydrate, 2 g by mouth, three times per day. Nine of ten patients who were able to take the full amoxicillin regimen were cured; among five patients treated with a lower daily amoxicillin dosage because of gastrointestinal (GI) side effects, only two were cured (P less than .05). The mean serum amoxicillin concentration at termination of therapy was higher (P less than .01) in five patients who were cured (10.4 +/- 1.6 microgram/ml) than in the four who failed (3.0 +/- 0.7 microgram/ml), although the latter values were all above the minimal inhibitory concentrations for infecting organisms. This study suggests that amoxicillin treatment of chronic typhoid carriers could be enhanced by treating with doses sufficient to provide suprainhibitory serum concentrations of the antibiotic. However, GI intolerance to amoxicillin could limit this therapeutic approach.