This study reports the detection of an extracellular staphylococcal product, designated secretory inhibitor of platelet microbicidal protein (SIPMP), that causes local inhibition of the bactericidal action of platelet microbicidal protein (PMP) in the fluid phase. Urethral isolates of Staphylococcus aureus (n=24) and coagulase-negative staphylococci (CNS) (n=47) from patients with or without chronic bacterial prostatitis (CBP) were tested. SIPMP production was tested by inhibition of PMP bioactivity against Bacillus subtilis and was expressed as percentage inhibition of PMP bactericidal activity. The PMP susceptibility of staphylococcal strains was determined by exposing bacterial cells to serial dilutions of PMP. Staphylococci from patients without CBP produced SIPMP at levels of 10.3+/-1.2 and 13.25+/-1.72 % for S. aureus and CNS, respectively. Strains isolated from men with CBP inhibited PMP-induced killing of B. subtilis by 23.38+/-4.2 % (P<0.05) and 23.69+/-1.87 % (P<0.01) for S. aureus and CNS, respectively. SIPMP production correlated with staphylococcal resistance to PMP (r2=0.6082 and 0.7264 for S. aureus and CNS, respectively). SIPMP represents a hitherto unrecognized determinant of staphylococcal pathogenicity. These results suggest that SIPMP production is associated with the CBP source. Data from this study may have significant implications for the understanding of the pathogenesis of CBP.