The susceptibility to ampicillin and trimethoprim-sulfamethoxazole (TMP-SMZ) was determined for 15,824 isolates of Shigella obtained from patients attending a treatment center in Dhaka, Bangladesh, from 1983 through 1990 and for 520 isolates obtained during community surveys from 1988 through 1990. Susceptibility to nalidixic acid was determined for isolates obtained after 1985. In 1983 13% of isolates were resistant to ampicillin, 23.5% to TMP-SMZ, and 0.8% to both drugs. By 1990 51.2% of isolates obtained at the Diarrhea Treatment Centre were resistant to ampicillin, 47.7% to TMP-SMZ, and 40.5% to both drugs (for comparison with figures for 1983, P less than .001). Resistance to nalidixic acid increased from 0.8% in 1986 to 20.2% in 1990 (P less than .001). In 1990 71.5% of Shigella dysenteriae type 1 isolates were resistant to ampicillin, 68.5% to TMP-SMZ, 67.7% to both drugs, and 57.9% to nalidixic acid. The resistance pattern of isolates obtained during community surveillance was similar to that of Treatment Centre isolates. In Bangladesh ampicillin and TMP-SMZ are no longer useful for treatment of infection with any species of Shigella, and nalidixic acid is no longer useful for treatment of infections due to S. dysenteriae type 1.