The preventive effect of penicillin V (pcV) in pneumococcal otitis media in the rat has been studied. The pcV was administered either before bacterial challenge (prevention group) or after challenge but before the establishing of acute purulent otitis media (AOM) (early treatment group). In both cases a fulminant infection was avoided. Thus, in the prevention group no animal developed AOM and in the early treatment group the fulminant AOM was avoided in all cases. These results give further support to the idea of using long-term treatment with an antibiotic with a narrow spectrum to avoid recurrent AOM (rAOM). Furthermore the observation that early treatment might stop the development of fulminant AOM indicates another more restrictive possibility to use antibiotic as a prophylactic measure in otitis-prone children.