Sexual dimorphism exists in the immune response. Both humoral and cell-mediated immunity are more active in females than in males, and steroid gonadal hormones may play an important role in regulating this response. We have documented gender differences in several aspects of neutrophil and macrophage functions elicited by lipopolysaccharide (LPS) (endotoxin) treatment and/or acute ethanol intoxication. In LPS-treated female rats, circulating neutrophils and alveolar macrophages are resistant to the deleterious effects of surgery and anesthesia on phagocytosis observed in male rats. The generation of cytokine-induced neutrophil chemoattractant (CINC) by hepatocytes and Kupffer cells of LPS-treated rats, as well as TNF-alpha secretion by Kupffer cells and alveolar macrophages of acutely ethanol intoxicated rats are also gender dependent. The effects of alcohol on the immune response are expressed differently in males and females. In LPS plus ethanol-treated rats gender differences were noted in terms of adhesion molecule (CD11b/c) expression on circulating neutrophils, and cytoskeletal reorganization in blood-recruited neutrophils and Kupffer cells. Nitric oxide (NO) plays an important role in inflammatory processes. We found gender differences in NO production by alveolar macrophages of LPS-treated rats; this difference was abrogated by ethanol treatment. LPS tolerance and ethanol treatment modulate hepatic NO production in rats in a cell- and gender-dependent fashion, which may exert a protective influence against oxidative injury in the female liver.