Continuous nationwide surveillance of antibiotic resistance in invasive pneumococcal disease was performed in Germany between 1992 and 2000, with a total of 2586 strains being isolated. The average resistance rates to erythromycin and clindamycin were 7.7% and 3.5%, respectively, throughout the study period; 3.3% of strains were found to have intermediate resistance to penicillin. Over the study period an increase in both macrolide and penicillin resistance was observed. The percentage of strains exhibiting reduced susceptibility to penicillin increased from 1.8% in 1992 to 5.8% in 2000. A dramatic increase in resistance was observed with erythromycin, where the resistance rate rose from 3.0% in 1992 to 15.3% in 2000. Of the erythromycin-resistant strains, 86 (43.4%) and 111 (56.1%) belonged to the erm(B) and mef types of resistance, respectively. An analysis of macrolide consumption data during the study period showed that erythromycin resistance was highly correlated to the consumption of newer bd and od macrolides (r = 0.89, P < 0.01).