In vitro surveillance data from across the United States indicate that approximately 10%-20% of urinary Escherichia coli isolates from female outpatients are resistant to trimethoprim-sulfamethoxazole (TMP-SMX). Alternative therapies for uncomplicated urinary tract infections in women include fluoroquinolones and nitrofurantoin, but the activities of these agents against TMP-SMX-resistant isolates are rarely reported. Among TMP-SMX-resistant urinary E. coli isolates tested in US laboratories from 1998 through 2001, 9.5% (5767 of 60,414) were resistant to ciprofloxacin and 1.9% (1214 of 63,817) were resistant to nitrofurantoin; 10.4% of ciprofloxacin-resistant isolates (683 of 6560) were resistant to nitrofurantoin. An association between resistance to fluoroquinolones and nitrofurantoin in E. coli has not been previously reported and warrants further study.