Three hundred eighty-six isolates of Propionibacterium sp. were recovered from 2,003 specimens studied for the identification of anaerobic bacteria in children during a 15-year period. Three hundred forty-three (89%) of these were Propionibacterium acnes. A total of 50 (13%) Propionibacterium isolates identified from 45 patients were considered to cause infection. Clinically significant infections caused by Propionibacterium sp. were associated with bacteremia in 10 children; ear infection in eight; abscesses in seven; adenitis and central nervous system infection in five each; burns in four; wounds in three; tumors and bone in two each; and cysts, eye, sinus, and mastoid in one each. Predisposing or underlying conditions were present in 33 children (73%). These included the presence of a foreign body (17), immunodeficiency (six), malignancy (five), diabetes (five), previous surgery (four), and steroid therapy (two). Antimicrobial therapy was given to 41 (91%) children. Surgical drainage was concomitantly performed in 22 (49%). Four patients died. This study highlights the importance of Propionibacterium sp. as an unusual, but potentially important, pathogen in children.