Inflammation has an important role in the development of chronic diseases. In this study, we evaluated the anti-inflammatory properties of eight soybean bioactive compounds using lipopolysaccharide-induced RAW 264.7 macrophages. Genistein, daidzein, a mix of isoflavone glucosides, saponin A group glycosides (saponin A), saponin B group glycosides (saponin B), sapogenol B, Bowman-Birk inhibitor (BBI), lunasin, and pepsin-pancreatin glycinin hydrolysates were tested by measuring their ability to inhibit cyclooxygenase-2/prostaglandin E(2) (PGE(2)) and inducible nitric oxide synthase (iNOS)/nitric oxide (NO) inflammatory pathways. Of the eight soy bioactive compounds (SBCs) tested, BBI and sapogenol B resulted in the highest inhibition of pro-inflammatory responses at a concentration 10 times lower than the one used for the other compounds. Also, sapogenol B and genistein (molar ratio 1:1) synergistically inhibited NO and additively inhibited PGE(2). Saponin A group glycosides showed inhibition of the iNOS/NO pathway only, while pepsin-pancreatin glycinin hydrolysates enhanced induction and production of the four inflammatory responses. For the first time, synergistic interactions were observed between BBI and genistein inhibiting NO (92.7%) and PGE(2) (95.6%) production. An antagonistic interaction was observed between the saponin B group glycosides and sapogenol B. All interactions were further confirmed by isobolographic analysis. These findings demonstrated that some SBCs possess anti-inflammatory properties and therefore are important in modulating mammalian inflammation pathways which may lead to inhibition of some types of chronic disease. Furthermore, through their interaction they can modulate the inflammatory process.