An outbreak of typhoid due to multi-drug resistant Salmonella typhi is reported from Pondicherry, India. While the average prevalence of drug resistant strains in 1980-1988 had been 11.7%, it increased to 52% in 1989-1990. The majority of strains (80.8%) were resistant to chloramphenicol, streptomycin, tetracycline and ampicillin; 40% were resistant to co-trimoxazole. Minimum inhibitory concentrations to 8 antibiotics for 17 representative strains were more than 10-fold greater than those of 13 sensitive strains. The multi-resistance was shown to be plasmid mediated in direct conjugation experiments and the strains belonged to Viphage type O, biotype II.