A surveillance program for invasive pneumococcal disease was undertaken in Puyde-Dĵme, an administrative district of the region Auvergne in France, from 1 January 1994 to 31 December 1998. A total of 214 cases were identified. The annual incidence of invasive pneumococcal disease increased (P=0.04) from 5.5 in 1994 to 9.3 cases per 10(5) person-years in 1998. The highest incidences were for children <2 years of age (59.2 cases per 10(5) person-years) and for adults > or = 65 years (18 cases per 10(5) person-years). Clinical diagnoses, available in 200 patients, included acute pneumonia (62%), meningitis (10%), sepsis without focus (20%), and others (8%). The most frequent chronic medical conditions of the patients included smoking, alcoholism, cardiovascular and pulmonary diseases, and malignancies. Thirty-one percent of the isolates were nonsusceptible to penicillin. Penicillin resistance (MIC > or = 0.1 mg/l) was more frequent (P=0.02) in cancer patients. The overall case-fatality rate was 21.5%. Risk factors for death were age, sex, and underlying diseases of the patients, along with the severity of illness. These population-based findings should convince clinicians to offer pneumococcal vaccine to patients at high risk for invasive pneumococcal disease, thereby increasing vaccination coverage levels in France.