Rats with catheter-induced aortic vegetations were challenged intravenously with various inoculum sizes of tolerant Streptococcus sanguis or Streptococcus faecalis. Single-dose amoxicillin (40 mg/kg) was given intravenously either 30 min before or 30-240 min after bacterial challenge. Prophylaxis of endocarditis against both strains was successful when the inocula used for challenge were in the range of the minimum inoculum producing bacterial endocarditis in 90% of control animals (ID90) but was less effective or failed with larger inocula or when amoxicillin administration was delayed up to 240 min after bacterial challenge with S. sanguis. In a group of rats profoundly depleted of neutrophils by a rabbit anti-rat neutrophil serum given 30 min after challenge with S. faecalis at ID90, single-dose amoxicillin administered simultaneously with the antiserum was protective, indicating that neutrophils were not required for successful endocarditis prophylaxis.