The frequency of occurrence of ESBL-producing clinical strains varies widely in distinct geographic areas. The objective of this study was to describe the frequency of occurrence, the preferred substrate, and the co-resistance patterns of the ESBL-producing isolates collected from the Asia-Pacific region and South Africa through the SENTRY Antimicrobial Surveillance Program between January 1998 and December 1999. A total of 1,377 Escherichia coli, 678 Klebsiella pneumoniae, and 138 Proteus mirabilis isolates were collected from diverse body sites. Using NCCLS criteria, 139 E. coli (10.1%), 171 K. pneumoniae (25.2%), and 2 P. mirabilis (1.4%) had presumptive ESBL phenotypes; 100, 146 and 1 strain respectively were confirmed to be ESBL producers on clavulanate enhancement testing. The frequency of occurrence of confirmed ESBL-producing E. coli by the medical centers varied from 0-1% for centers located in Australia to 13-35% for mainland Chinese centers. The higher prevalence rates (>20%) of ESBL K. pneumoniae phenotypes were observed in all mainland Chinese centers, one Japanese and one Taiwanese center, and in the Philippine, South African, Singaporean and medical centers. The spread of the presumptive ESBL phenotype to the Enterobacter species was observed in nine medical centers. Overall, ceftriaxone and aztreonam were the best substrates for the detection of the ESBL phenotype between both E. coli isolates and K. pneumoniae ESBL phenotypes; however, there was significant variation between countries in substrate preference. Co-resistances to gentamicin, tobramycin, tetracycline, and trimethoprim-sulfamethoxazole were common throughout isolates collected from most medical centers. Ciprofloxacin resistance rates were very high among isolates collected from Hong Kong, mainland China, Singapore, and the Philippines. The best coverage against ESBL-producing isolates was obtained with imipenem (0% resistance), followed by amikacin (6% resistance).