Eight hundred and sixteen isolates of Propionibacterium species (725 of which were Propionibacterium acnes) were isolated from 3,971 specimens submitted for the identification of anaerobic bacteria over the course of 10 years. A total of 94 Propionibacterium isolates (12%) identified in 92 patients were considered to cause infection. The rest of the isolates were determined to be contaminants or of uncertain pathogenic significance. Significant infections caused by Propionibacterium species were associated with the blood in 15 patients, central nervous system in 11, lymph glands in 10, abscesses in eight, joints in seven, wounds in seven, cysts in six, and sinuses in five. Predisposing or underlying conditions were noted in 66 patients (70%). The most common conditions were the presence of foreign bodies (29 patients), diabetes (12), previous surgery (10), trauma (seven), malignancy (seven), immunodeficiency (seven), and steroid therapy (four). Antimicrobial therapy was administered to 83 patients; for 47 patients this therapy was given in conjunction with surgical drainage or correction. Surgical drainage alone was performed in nine patients. Five patients (5%) died. These data illustrate that although Propionibacterium species are rarely associated with infections, these organisms can occasionally cause serious infections.