Objective: To determine the effect of peak inspiratory pressure (PIP) and positive end-expiratory pressure (PEEP) on the development of bacteremia with Klebsiella pneumoniae after mechanical ventilation of intratracheally inoculated rats. Design: Prospective, randomized, animal study. Setting: Experimental intensive care unit of a University. Subjects: Eighty male Sprague Dawley rats. Interventions: Intratracheal inoculation with 100 mu l of saline containing 3.5-5.0 x 10(5) colony forming units (CFUs) K. pneumoniae/ml. Pressure-controlled ventilation (frequency 30 bpm; I/E ratio = 1:2, FIO2 = 1.0) for 180 min at the following settings (PIP/PEEP in cmH(2)O): 13/3 (n = 16) 13/0(n = 16); 30/10 (n = 16) and 30/0 (n = 16), starting 22 h after inoculation. Arte rial blood samples were obtained and cultured before and 180 min after mechanical ventilation and immediately before sacrifice in two groups of non-ventilated control animals (n = 8 per group). After sacrifice, the lungs were homogenized to determine the number of CFUs K. pneumoniae. Measurements and results: The number of CFUs recovered from the lungs was comparable in all experimental groups. After 180 min, 11 animals had positive blood cultures for K. pneumoniae in group 30/ 0, whereas only 2, 0 and animals were positive in 13/3, 13/0 and 30/10, respectively (p < 0.05 group 30/0 versus all other groups), Conclusions: These data show that 3 h of mechanical ventilation with a PTP of 30 cmH(2)O without PEEP in rats promotes bacteremia with K. pneumoniae. The use of 10 cmH(2)O PEEP at such PIP reduces ventilation-induced K. pneumoniae bacteremia.