Appropriate antibiotic treatment of shigellosis depends on identifying resistance patterns. By studying Shigella isolates in central Israel from 1998 to 2000, and comparing with the period 1991-1992, we identified a significantly increased resistance to tetracycline (from 23% to 87%, P < 0.00001), high resistance to trimethoprim-sulfamethoxazole (94%) and ampicillin (85%) and emerging resistance to quinolones (0.5-2%). These data mandate local monitoring of resistance and its consideration in empirical therapy.