Numerous cardiac disease processes have been linked to the overproduction of nitric oxide (NO) via inducible nitric oxide synthase (iNOS) in the cardiovascular system. Chronic and acute exposure to hyperphysiologic levels of NO has been suggested as an agent in chronic transplant rejection, various cardiomyopathies, reperfusion injury, and the inflammatory state following cardiopulmonary bypass. Proinflammatory cytokines and inflammatory cell types, such as macrophage and neutrophils, have also been implicated in the pathophysiology associated with the previously mentioned syndromes. Previous work by this group has shown that lipopolysaccharide (LPS) in combination with tumor necrosis factor-alpha (TNF-alpha) can increase iNOS expression and the production of NO in macrophage. With this in mind, we hypothesized that increased iNOS expression and NO production generated by LPS and TNF-alpha in the macrophage could be mimicked in the cardiomyocyte and potentially account for some aspect of the cardiac dysfunction attributed to NO. Furthermore, this increased expression of iNOS and NO production could be returned to control using the glucocorticoid, dexamethasone, a known iNOS transcription blocker. Using fetal rat cardiomyocytes in primary culture cell line and a murine macrophage cell line, RAW 264.7, the expression of iNOS was quantified with specific FITC-conjugated antibodies using fluorescence activated cell sorter (FACS) and NO production with a Bioxytech nitric oxide spectrophotometric assay. The myocytes and macrophage were separated into three groups, Control, TNF + LPS, and (+) Dexamethasone. The control groups received no TNF or LPS or dexamethasone, TNF + LPS groups received TNF-alpha and LPS for 8 hours with no dexamethasone, and the (+) Dexamethasone groups were pretreated with dexamethasone for 8 hours and stimulated with TNF-alpha and LPS along with a second 8-hour treatment of dexamethasone. The macrophage cell groups treated with TNF-alpha and LPS showed a 335% increase over control in iNOS expression, and NO production was increased 494% from control. Macrophage treated with dexamethasone experienced an attenuation of iNOS expression of 200% toward control from stimulated levels and 202% decrease in NO production from stimulated levels toward control. Cardiomyocytes exhibited no statistically significant change in the expression of iNOS or NO production with stimulation or dexamethasone treatments. In conclusion, iNOS and NO were elevated in macrophage, which can be blunted in the presence of dexamethasone in the macrophage. Curiously, iNOS could not be stimulated in the cardiomyocyte, suggesting inflammatory cells may be largely responsible for the elevated iNOS and NO experienced in some cardiovascular diseases. The clinical relevance of this study is the introduction of specific iNOS inhibitors into the cardiopulmonary bypass circuit could serve as a potential mechanism for modulating the inflammatory response surrounding cardiopulmonary bypass. Likewise, therapeutic glucocorticoid administration could improve outcomes for patients with inflammatory cardiovascular disease states related to elevated NO production.