HIV-1 causes lung disease by increasing the host's susceptibility to pathogens. HIV-1 also causes an increase in systemic oxidative/nitrosative stress, perhaps enhancing the deleterious effects of secondary infections. Here, we have examined the ability of HIV-1 proteins to increase lung oxidative/nitrosative stress following lipopolysaccaride (LPS) (endotoxin) administration in an HIV-1 transgenic mouse model. Lung oxidative/nitrosative stress biomarkers studied 3 and 6 hours post LPS administration were as follows: lung edema, tissue superoxide, nitric oxide (NO) metabolites, nitrotyrosine, hydrogen peroxide, and bronchoalveolar lavage fluid (BALF) glutathione (GSH). Blood serum cytokine levels were quantified to verify immune function of our non-immuno-compromised animal model. Results indicate that 3 hours post LPS administration, HIV-1 transgenic mice lung tissue has significantly greater edema, superoxide. Furthermore, NO metabolites are significantly elevated in HIV-1 transgenic mice BALF, lung tissue and blood plasma compared to wild type mice. HIV-1 transgenic mice also produce significantly greater lung nitrotyrosine, and hydrogen peroxide in comparison to wild type mice. In addition, HIV-1 transgenic mice produce significantly less BALF GSH in comparison to wild type 3 hours post LPS treatment. Without treatment, serum cytokine levels are similar for HIV-1 transgenic and wild-type mice. After treatment, serum cytokine levels are significantly elevated in both HIV-1 transgenic and wild-type mice. Therefore, HIV-1 transgenic mice have significantly greater lung oxidative/nitrosative stress following endotoxin administration compared to wild type mice, independent of immune function. These results indicate that HIV-1 proteins may increase pulmonary complications subsequent to a secondary infection by altering the lung redox potential.