Four hundred and fifty-two urine isolates from women with acute uncomplicated cystitis and a positive urine culture presenting to a sexually transmitted disease clinic were collected during 1989-1991, and 213 specimens were collected over 1995-1997. The predominant species was Escherichia coli, representing 68% of the isolates; others included Staphylococcus saprophyticus (8%), Group B streptococci (7%), Proteus spp. (6%), Klebsiella spp. (4%) and Enterococcus spp.(3%). More than 10% of the E. coli isolates were resistant to ampicillin, cephalothin, tetracycline and trimethoprim sulfamethoxazole (TMP SMX ) during both study periods, with the greatest increase in resistance to ampicillin and TMP/SMX between the two periods. Six hundred and four urinary tract infection isolates, including 83% E. coli, 7% S. saprophyticus, 3%, Klebsiella spp. 2% Proteus spp., 2% enterococci, 1% Enterobacter spp. and 2% other organisms, were collected from women with acute cystitis attending a university student health service during 1995. Among E. coli isolates, 25% were resistant to ampicillin, 24% to tetracycline and 11%, to TMP SMX. Resistance to fluoroquinolones was essentially absent among gram-negative pathogens. Continued evaluation of susceptibility patterns of pathogens causing acute uncomplicated cystitis to traditional as well as new antimicrobials in well defined populations is necessary to ascertain the optimal empiric therapy.