Resistance of Streptococcus pneumoniae (750) to penicillin, erythromycin, chloramphenicol and trimethoprim/sulfamethoxazole isolated in 4 Turkish hospitals between 1996 and 1999 was evaluated according to year of isolation, patients' age groups and specimen. Penicillin susceptibility was determined by E-test strips and the other antibiotics were tested by disk diffusion test following the NCCLS guidelines in each center. Overall high and intermediate resistance to penicillin was 3% and 29%, respectively. There was a significant difference (p <0.001) between the centers with regard to penicillin resistance. However, there was no significant increase in resistance by year. Penicillin resistance varied significantly among children and adults (36% versus 25%) and according to the specimen. Highest rate of penicillin resistance was observed in respiratory specimens (36%) followed by ear exudates (33.5%). In blood isolates, resistance to penicillin was 28.6%. Overall resistance to erythromycin was 8%, to chloramphenicol 5% and to trimethoprim-sulfamethoxazole 47%. Although overall penicillin resistance in these Turkish S. pneumoniae isolates is high, resistance rates vary in each center and have not increased from 1996 to 1999.