In the United States, trimethoprim-sulphamethoxazole (TMP-SMX) is the recommended first-line treatment for uncomplicated urinary tract infections (UTIs) in females, in regions with resistance rates of <10-20%. Unfortunately, current data on regional resistance is often not readily available to physicians and regional variability in resistance remains largely unknown. This report presents antimicrobial susceptibility data for TMP-SMX and three other commonly tested antimicrobials organized by state and region to demonstrate current regional variability in resistance in the US. In the last quarter of 1999, 5739 fresh clinical isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Staphylococcus saprophyticus were collected from 202 laboratories throughout the US. Susceptibility testing was performed against TMP-SMX, cephalothin, nitrofurantoin and ciprofloxacin using broth microdilution. Data were analyzed by patient age and specimen source, and by state and region. In the US as a whole, resistance to TMP-SMX was 16.8% for E. coli, 7.8% for K. pneumoniae, 12.1% for P. mirabilis and 3.0% for S. saprophyticus, but these rates showed considerable regional variation. By state, E. coli resistance ranged from 7.4% in Pennsylvania to 33.3% in Iowa (among states with > or =50 isolates tested). Regionally, resistance for all uropathogens taken together ranged from 8.5% in East South-Central to 22.8% in West South-Central. Ciprofloxacin demonstrated the broadest activity of the antimicrobials tested and was more active than TMP-SMX against all pathogens. Resistance to TMP-SMX among E. coli now approaches or exceeds 20% in some areas. As resistance among uropathogens reaches clinically significant levels in many areas, continued regional surveillance is essential to ensure the provision of effective empiric therapy for urinary tract infections.