To assess trends in antimicrobial-resistant Salmonella infections from 1989 to 1996 in southern Taiwan, the minimum inhibitory concentrations (MICs) of 14 antibiotics or antibiotic combinations were determined by the agar dilution method for 297 clinical isolates of nontyphoidal Salmonella. The rates of resistance to ampicillin, chloramphenicol, and tetracycline were 65, 67, and 78%, respectively. Resistance to trimethoprim-sulfamethoxazole (TMP-SMX) increased from 25% in 1989-1992 to 35% in 1993-1996 (P=0.057). For new quinolones and extended-spectrum cephalosporins, no resistant strains were encountered. Multiple resistance to more than five antimicrobial drugs doubled from 10.6% in 1989-1992 to 19.7% in 1993-1996. Multiply resistant salmonellae were isolated more commonly from blood samples than from feces (30% vs. 14%, P<0.05). In Taiwan, ampicillin, chloramphenicol, and even TMP-SMX are no longer the drugs of choice for treatment of serious nontyphoidal Salmonella infections. Extended-spectrum cephalosporins are now the preferred drugs in Taiwan for treatment of invasive Salmonella infections in children.