Over the last two decades, antimicrobial resistance in Streptococcus pneumoniae has been detected at an increasing rate. There have been several reports of increasing rate of macrolide resistance among the penicillin-resistant S. pneumoniae strains. The rapid evolution of such resistance necessitated new antimicrobials, such as streptogramins, oxazolidinones and ketolides, against beta-lactam and macrolide resistant pneumococci. This study was undertaken to determine the prevalence of macrolide resistance in pneumococci isolated in a Turkish University hospital and also to determine the activity of these newly developed agents against pneumococci. For that purpose a total of 264 pneumococci, isolated from clinical specimens, were tested for susceptibility against penicillin, erythromycin, clarithromycin, clindamycin, quinupristin/dalfopristin, linezolid and telithromycin by agar dilution method. Penicillin resistance and intermediate penicillin resistance was found in 7.6% and 40% of isolates respectively, while resistance rates of the tested isolates against erythromycin, clarithromycin and clindamycin were as 15.9%, 13.6% and 13.6%, respectively. Resistance to macrolides and clindamycin was higher among the penicillin-resistant isolates. No resistance was detected against quinupristin/dalfopristin, linezolid and telithromycin, except for four strains which had minimal inhibitory concentration (MIC) values of intermediately susceptible category to quinupristin/dalfopristin. These data indicate the presence of an important percentage of macrolide resistant pneumococci in our hospital. It can also be concluded that streptogramins, oxazolidinones and ketolides may be used as good alternatives especially in case of infections due to macrolide resistant pneumococci.