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Outbreaks of Shigella dysenteriae I occurred in northeastern Thailand in the fall of 1986 and again in the spring and fall of 1987 for the first time in over 20 years. The epidemic strain of S. dysenteriae I was resistant to tetracycline, streptomycin, chloramphenicol, and trimethoprim-sulfamethoxazole, but susceptible to ampicillin. Trimethoprim resistance was chromosomally encoded by type I dihydrofolate reductase. In Ubon Province, where 10,000 cases of dysentery were reported, there were 3–5 cases of dysentery per 1,000 residents during the peak months, with 2–5 hospitalizations per 100 cases of reported dysentery. There were 2 deaths among 101 hospitalized, culture-confirmed cases. The overall case-fatality rate among reported cases of dysentery in this province was 0.9%. In contrast to S. flexneri infections, which occurred predominantly among children <5 years old, S. dysenteriae I infections occurred in all age groups. The large number of susceptibles appeared to be important in allowing rapid spread of S. dysenteriae I. In 1 village, 46% of 434 villagers reported dysentery; S. dysenteriae I was isolated from 24 out of 81 (30%) individuals cultured. Based on the prevalence of IgG antibody to S. dysenteriae I lipopolysaccharide, it was estimated that 76% of the villagers had been infected.