Neointimal hyperplasia (NH) is the most significant contributing factor to long-term vascular graft failure. Inflammation is known to be important in its development; however, the role of bacterial infection is unclear. We examined the effect of contamination with common organisms on the development of NH in expanded polytetrafluoroethylene grafts. Thirty adult pigs were randomized into one of four groups: no infection, contamination with Staphylococcus aureus, mucin-producing Staphylococcus epidermidis, or Pseudomonas aeruginosa. An expanded polytetrafluoroethylene graft (6 mm x 3 cm) was placed as a common iliac artery interposition graft and was inoculated with 1-2 x 10(8) of the selected organism before closure. Grafts were explanted 6 weeks postoperatively. Microbiologic, histological, and morphometric evaluations were performed. All grafts were patent at the time of euthanasia. The mean areas of NH were 5.45 mm(2) in sterile grafts, 8.36 mm(2) in S. aureus, 7.63 mm(2) in S. epidermidis, and 11.52 mm(2) in P. aeruginosa grafts. Comparison of means via analysis of variance showed that P. aeruginosa grafts had significantly higher formation of NH than sterile grafts (P = 0.025). NH production in infected grafts appears to be organism specific and is significantly higher with P. aeruginosa than common Gram-positive organisms. Increased NH from subclinical infection may be a significant factor contributing to late graft failures.