Aims: This study was undertaken to determine the antimicrobial resistance patterns of strains of Streptococcus pneumoniae from Sydney, Australia, comparing penicillin-susceptible, - intermediate and - resistant isolates. Methods: Non-duplicate cultures of S. pneumoniae were collected from 1 January to 31 December 2002 in the three penicillin-susceptibility categories. Minimum inhibitory concentrations ( MICs) of 19 antibacterial agents were determined by agar dilution based on the National Committee for Clinical Laboratory Standards (NCCLS) methodology. Overall for 2002, 687 non-duplicate isolates were obtained, of which 190 (28%) were intermediate or resistant to penicillin. From this set, 183 isolates were selected for study: 88 (48%) in the penicillin- susceptible group ( MIC <= 0.06 mg/ L), 25 ( 14%) in the penicillin- intermediate group ( MIC 0.125 - 1.0 mg/ L) and 70 ( 38%) in the penicillinresistant group ( MIC >= 2.0 mg/ L). Results: Resistance to non- beta- lactams was more common in penicillin- intermediate or - resistant strains. Multidrug resistance ( resistance to >= 2 non-beta-lactams) was found in 3% of penicillin- susceptible, 52% of penicillin- intermediate and 87% of penicillin- resistant isolates. Erythromycin resistance was seen in 22% of the penicillin- susceptible strains but increased significantly to 60% and 89% in the penicillinintermediate and resistant strains, respectively. Clindamycin, tetracycline and trimethoprim/ sulfamethoxazole showed similar diminished activity in penicillin- intermediate and - resistant strains; 64, 84 and 91% of the penicillin- resistant isolates were resistant to clindamycin, tetracycline and to trimethoprim/ sulfamethoxazole, respectively. Chloramphenicol resistance was comparatively low level except 19% of the penicillin- resistant strains were resistant. Ciprofloxacin MICs for 14 strains were raised ( MICs 4 16 mg/ L); three of these were penicillin- susceptible, one penicillin- intermediate and 10 penicillin- resistant. Only one isolate was resistant to moxifloxacin and to gatifloxacin. Resistance to rifampicin, vancomycin, oritavancin, or linezolid was not detected. Twenty- three isolates were intermediate and one resistant to quinupristin/ dalfopristin - 22 of these were penicillin resistant. Conclusions: Streptococcus pneumoniae isolates from Sydney are commonly resistant to beta- lactams and available non- b- lactam agents, especially if they are penicillin nonsusceptible. Resistance to moxifloxacin and gatifloxacin still rare, but some isolates were non- susceptible to quinupristin/ dalfopristin. It is important to continue to survey resistance patterns to recognise emerging resistances which affect the selection of empirical antimicrobials to treat infections with S. pneumoniae.