The proportion of infective endocarditis (IE) caused by group D streptococci (GDS; formerly Streptococcus bovis) increased markedly in France, to account for 25% of all cases of IE by 1999. In an attempt to explain this phenomenon, a comparative analysis of GDS and oral streptococci (OS) causing IE was performed. This study was based on data collected from a large cross-sectional population-based survey that was conducted in 1999. In total, 559 cases of definite IE were recorded, of which 142 involved GDS and 79 involved OS. Patients with GDS IE were older (62.7 vs. 56.6 years, p 0.01) and had a history of valve disease less frequently than did patients with OS IE (33.8% vs. 67.1%, p <0.0001). At-risk procedures for IE were performed less frequently in patients with GDS than in patients with OS (14.8% vs. 24.1%, p 0.08), but co-morbidities were more frequent in the GDS group (59.9% vs. 32.9%, p 0.0001). Diabetes, colon diseases and cirrhosis were also more frequent in the GDS group (p 0.006, p <0.0001 and p 0.08, respectively). Rural residents accounted for 31.0% of the GDS group, but for only 15.2% of the OS group (p 0.001). Likewise, the proportion of GDS IE was higher in regions with mixed (urban and rural) populations (Franche-Comté 81.8%, Marne 68.7%, Lorraine 70.3% and Rhône-Alpes 65.3%) than in exclusively urban regions (Paris and Ile de France 58.0%). Further investigations are required to elucidate the link in France between the incidence of GDS IE, rural residency and nutritional factors.