Macrolides are widely used in the treatment of respiratory infections. Here, the authors compared the activity of different 14-membered macrolides: erythromycin (Ery), roxithromycin (Rox), clarithromycin (Cla) and its 14-hydroxy metabolite 14-OH clarithromycin (14-OH) against 30 strains of Streptococcus pneumoniae isolated at the Dupuytren hospital (Limoges, France) from upper respiratory tract sputum, ophthalmic sputum, blood samples and CSF. Twenty strains were susceptible to macrolides and 10 were resistant. Three strains from the susceptible and 7 from the resistant were resistant to penicillin. Furthermore, for all the macrolides except Rox and 14-OH, susceptibility tests were performed by the disk diffusion method on Mueller-Hinton agar. MICs50 of Cla and Ery were 0.06 mg/l. They were two-fold increased for 14-OH (0.125 mg/l) and four-fold increased for Rox (0.25 mg/l). We noted that for 3 resistant strains, MICs of Cla were four-fold decreased than MICs of Ery. Ery, Cla and 14-OH had bactericidal activity against pneumococcus strains susceptible to these antibiotics at 4 and 8 times the MIC after 6 or 18 h. The difference between MIC and MBC was small (1 or 2 two-fold dilutions) for Ery, Rox and Cla. For 14-OH, this difference was within 2 to 4 two-fold dilutions. The bactericidal activity is similar to that of amoxicillin and cefotaxim. A microdilution chequeboard technique was used against 3 strains and the FIC index did not show synergistic effect of combining Cla and 14-OH. The activity of Cla and 14-OH against 5 strains was not modified in the presence of 50% fresh pooled human serum inactivated at 56 degrees C or not.