We determined the MBC of amoxicillin and vancomycin, two antibiotics advocated for treatment and prophylaxis of bacterial endocarditis, for 24 strains of viridans group streptococci isolated from patients with endocarditis. We found that the MIC of amoxicillin for all strains was less than or equal to 0.25 micrograms/ml and the MBC was either low (less than 0.5 micrograms/ml) in 6 nontolerant strains or high (greater than 128 micrograms/ml) in 18 tolerant strains. The MIC of vancomycin for the 24 strains was less than or equal to 1 microgram/ml, and the MBC was either low (less than 1 microgram/ml) for 3 nontolerant strains or high (greater than 128 micrograms/ml) for 21 tolerant strains. In addition to the MBC, we determined the actual reduction of the viable bacterial counts in each tube dilution after 24 h of incubation. This determination was made by subtracting the number of colonies observed on the subculture plate from the number of bacteria contained in the initial inoculum. For both antibiotics we found that the maximal reduction in viable counts was achieved at or very close to the MIC and did not increase with increasing antibiotic concentrations (up to 128 micrograms/ml). As expected, the six strains for which the amoxicillin MBC was less than 0.5 micrograms/ml and the three strains for which the vancomycin MBC was less than 1 microgram/ml had a reduction of viable counts of more than 3 log10 (greater than 99.9% killing). In contrast, among the strains defined as tolerant to amoxicillin and vancomycin, there were wide variations in the actual reduction of bacterial counts, ranging from 3 log10 to less than 1 log10. Therefore our observations suggest that the reduction of viable streptococcal counts reflects more accurately the bactericidal effect of amoxicillin and vancomycin than does the MBC, which artificially divides the strains into sensitive or tolerant strains.