Recent (1984 to 1992) trends in the antimicrobial resistance of Shigella isolates in Israel were studied by analyzing the results of 106,000 stool cultures, 3,511 of which yielded Shigella spp. Over the study period, resistance to trimethoprim-sulfamethoxazole (TMP-SMX) increased from 59 to 92% (P = 0.0038) and that to ampicillin increased from 13 to 86% (P < 0.0001). Resistances to nalidixic acid, chloramphenicol, and broad-spectrum cephalosporins remained low. Shigella sonnei, which currently accounts for 90% of Shigella infections, was more resistant than S. flexneri to TMP-SMX (81 versus 57%, P < 10(-6)), ampicillin (42 versus 32%, P < 10(-5)), and tetracycline (38 versus 28%, P < 10(-5)). S. boydii and S. dysenteriae were relatively rare. Seasonality in antimicrobial resistance was found, with summer isolates being less resistant to TMP-SMX, ampicillin, or both than isolates obtained over the rest of the year (P < 10(-5)). We conclude that the resistance of shigellae, especially S. sonnei, to TMP-SMX and ampicillin is increasing to approximately 90%. Resistance should be recorded locally, and empiric therapy for suspected shigellosis should be changed accordingly.