A population-based survey of invasive pneumococcal disease (IPD) was conducted among adults in North-Rhine Westphalia, Germany. The study included 202 of the 386 hospitals in the region, together with the 27 microbiological laboratories that submitted reports of IPD in these hospitals to the National Reference Centre for Streptococci. The reports of 16 laboratories were comprehensively reviewed. Most (95.8%) IPD isolates were susceptible to penicillin G, but 14.5% were resistant to clarithromycin. Serotypes 14 (15.6%), 3 (9.3%), 4 (7.1%) and 7F (7.9%) were the most common. The serotype coverage of the 23-valent pneumococcal polysaccharide vaccine was 80.8%. During 2001-2003, the annual incidence of IPD, after correcting for laboratory and hospital under-reporting, was 16.2/100 000 in individuals aged >or= 65 years. In three university hospitals, blood cultures were obtained for only 37% of patients with community-acquired pneumonia, and fewer than one-third of such cultures were obtained in one hospital before antibiotics were prescribed, suggesting that the true incidence of IPD was closer to 50/100 000.