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Antimicrobial agents still remain the mainstay in the treatment of enteric fever; however, indiscriminate use of these drugs has led to the emergence of resistance in Salmonella typhi. Many reports are available on drug resistance in S. typhi from different parts of India,1 but there is no report available from the eastern part of northern India. There are reports from India that ciprofloxacin has begun to produce delayed clinical responses in enteric fever2 with gradual increases in MICs of ciprofloxacin3 and clinically quinolone-resistant typhoid fever.4 The present study was conducted to investigate the pattern of drug resistance in isolates of S. typhi obtained between 1979 and 1998 in the University Hospital of Banaras Hindu University, Varanasi, with special reference to ciprofloxacin. A total of 140 isolates of the bacterium were tested for antimicrobial susceptibility by agar diffusion and 59 isolates, selected randomly, were subjected to MIC determinations of ciprofloxacin by the agar dilution method as recommended by NCCLS (1997).5 Plasmids from the three ciprofloxacin-resistant isolates were obtained with a Qiagen-QIA prep spin Miniprep Kit and transformation studies were carried out in Escherichia coli (DH5α).