Since 1987, multidrug resistant (MDR) strains of Salmonella Typhi, resistant simultaneously to ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole, have caused epidemics of severe typhoid fever in Asia and Africa. A retrospective analysis of blood culture results (1989–96) in a Diarrhoea Treatment Centre in Dhaka, Bangladesh detected MDR strains in 0.3% (8 of 2793) of samples in 1990. The isolation rate peaked to 3.2% (240 of 7501) in 1994 (P<0.01) and decreased to 1.8% (165 of 9348) in 1995 and further to 1.0% (82 of 8587) in 1996 (P<0.01 compared to 1994) indicating the emergence and decline of MDR typhoid epidemic. Ten of 15 MDR strains tested had a 176 kb conjugative R plasmid that mediates resistance to ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole to Escherichia coli K12. Unlike MDR strains, the isolation rate (∼3.3%) of susceptible S. Typhi remained remarkably unchanged during the study. The significant decrease in isolation of MDR strains suggests that cheaper and effective first-line antibiotics may re-emerge as drugs of choice for the treatment of typhoid fever in Bangladesh.