The presence of K1 capsular polysaccharides increases the resistance of Escherichia coli to killing by serum and phagocytosis by polymorphonuclear leukocytes (PMNs). To determine whether K1 capsule impedes the action of intracellular bactericidal systems of PMNs, we compared the sensitivity of several K1-encapsulated and non-encapsulated strains of E. coli to killing by the bactericidal/permeability-increasing protein (BPI) isolated from rabbit and human PMNs. BPI appears to be the principal bactericidal agent of PMNs toward E. coli and other gram-negative bacteria (Weiss et al., J. Clin. Invest. 69:959-970, 1982). The presence of K1 capsule was monitored by sensitivity to K1-specific bacteriophages. The non-encapsulated strains used represent both random bacteremic isolates and non-encapsulated derivatives of K1-encapsulated strains obtained by selection for resistance to K1-specific phages. We found little or no difference in the sensitivity of K1-encapsulated and non-encapsulated E. coli to killing by neutralized acid extracts of rabbit PMNs. Bacterial killing by these crude fractions can be attributed to the action of BPI because: (i) bacterial killing was blocked by immune (anti-BPI) immunoglobulin but not by preimmune immunoglobulin and (ii) comparison of the dose-response curves of bacterial killing by crude extracts and by purified BPI showed that the bactericidal activity of crude fractions corresponded closely to the BPI content. Human and rabbit BPIs exhibited similar bactericidal potency toward K1-encapsulated E. coli; i.e., <5 mug of either protein killed >90% of 2.5 x 10(7) bacteria. Thus, the potent bactericidal action of BPI toward E. coli is not impeded by K1 capsule, suggesting that the virulence of K1-encapsulated E. coli is a consequence of extracellular survival but not of resistance to intracellular killing.