In order to establish a human challenge model of Shigella related disease for vaccine testing, a dose-escalating inpatient trial was performed. Three groups of 12 healthy adult volunteers were orally challenged with 93,440 and 1680 CFU of Shigella sonnei strain 53G. Subjects were admitted to the Vaccine Trial Centre (VTC) at Mahidol University in Bangkok, Thailand. The primary purpose of this study was to identify the dose of S. sonnei 53G required to elicit clinical disease in at least 70% of Thai adult subjects. At the highest dose of 1680 CFU, the attack rate was 75%, while at the two lower doses, the attack rate was approximately 50%. This human challenge model, which is the first of its kind in an endemic region, will provide an opportunity for S. sonnei vaccine evaluation in endemic populations.