Between January 2000 and March 2001, Streptococcus pneumoniae were isolated from the blood of 56 patients admitted to a single district general hospital in the South-East of England. The serotype and antibiotic susceptibility were determined for all isolates and, for those resistant to erythromycin, the presence or absence of the mef(A) and erm(B) genes was determined by PCR. Multi-locus sequence typing, along with PFGE, was undertaken on all isolates resistant to penicillin or erythromycin and a group of antibiotic-susceptible isolates, to identify whether globally distributed pneumococcal clones, as described by the Pneumococcal Molecular Epidemiology Network (PMEN), were present in the study population. Three serotype 9V penicillin-resistant isolates were identified as belonging to the Spain9V-3 clone, while 14 erythromycin-resistant isolates of serotype 14 belonged to the England 14-9 clone. A single multi-resistant isolate of serotype 6B, was found to be a single-locus variant of the Spain6B-2 clone. All 14 erythromycin-resistant serotype 14 isolates possessed the mef(A) gene, while the single multi-resistant isolate possessed the erm(B) gene. These findings confirm the wide distribution and clinical impact of PMEN clones, which accounted for all of the penicillin and erythromycin resistance observed amongst invasive isolates in a district general hospital over a 15-month period.