Traditionally, platelets have been thought to contribute to the induction and propagation of infective endocarditis (IE). However, recent studies suggest that platelets may potentially mitigate IE via secretion of alpha-granule-derived platelet microbicidal protein (PMP). In this study, we compared the PMP susceptibility of bacteremic isolates from patients with and without IE. Isolates of Staphylococcus aureus (n = 17), coagulase-negative staphylococci (CNS; n = 28), viridans streptococci (VS; n = 54), and Enterococcus faecalis (n = 20), each at a final inoculum of 2 x 10(3) CFU/ml, were exposed to PMP [100 U/ml, (5 micrograms/ml)] for 2 h, and the percent survival was determined. For S. aureus, CNS, and VS isolates, there was a significant correlation between an IE source and increased percent survival post-PMP exposure; the mean percent survivals of S. aureus, CNS, and VS were significantly greater for IE versus non-IE isolates (P < 0.005 for each organism). No significant correlation was observed between the source of bacteremic E. faecalis isolates and PMP susceptibility. These data suggest that staphylococcal and VS (but not enterococcal) resistance to PMP may facilitate either the induction or progression of IE.