In order to determine the current antibiotic susceptibility of Streptococcus pneumoniae strains in Greece, the present study was performed on 282 clinical isolates collected from patients at the Sotiria Chest Hospital of Athens, Greece, during the years 1997-2003. Susceptibility testing revealed that 52 (18.4%) isolates were not susceptible to penicillin, with 13.1% demonstrating intermediate and 5.3% high-level resistance. One of the penicillin-non-susceptible isolates was also resistant to cefotaxime. Comparison with results of a previous study conducted at the same hospital during the period 1992-1993 showed that penicillin resistance had increased by 4.5%. The results of this study indicate the antimicrobial susceptibility of Streptococcus pneumoniae continues to change in Greece and continuous surveillance remains important for guiding empirical antibiotic therapy.