Background Addition of 2% glutamine (GLN), a specific lymphocyte fuel, prevents deleterious effects of TPN on gut-associated lymphoid tissue and IgA while preserving IgA-mediated upper respiratory immunity to influenza virus. We examined whether a 2% GLN-enhanced TPN solution preserves respiratory immunity to a lethal and clinically relevant pneumonia challenge. Materials and methods. Male ICR mice were randomized to chow (n = 20), TPN (n = 20), or an isonitrogenous, isocaloric TPN-2% GLN solution (n = 17). All groups were immunized 10 days before surgery with Pseudomonas polysaccharide-containing liposomes (LIP) to confer immunity except for a nonimmune chow-fed LIP control group (n = 21) which received LIP without Pseudomonas. Mice received 5 days of diet and then were given an LD90 dose of 1.2 x 10(8) intratracheal Pseudomonas bacteria, and mortality was recorded, Results. Immunization reduced mortality compared with LIP alone. TPN impaired immunity and reduced survival while GLN maintained immunization effectiveness, [GRAPHICS] *P < 0.01 vs TPN. dagger P < 0.01 vs LIP. Conclusions. Pseudomonas immunization reduces mortality to Pseudomonas pneumonia, but this immunity is lost with TPN. Addition of 2% GLN to TPN preserves immunity in the respiratory tract and reduces mortality to a lethal bacterial challenge compared with standard TPN. (C) 1999 Academic Press.