Multidrug resistance in several strains of Vibrio cholerae has encouraged anti-cholera vaccine developmental attempts using various subcellular moieties. In order to examine the immunological efficacy of detoxified LPS (dLPS)-derived saccharide immunogens, ex vivo activation of mouse peritoneal macrophages (MPhis) was investigated. The immunomodulatory effect was evaluated via induction of the pro-inflammatory cytokines tumour necrosis factor-alpha, interleukin (IL)-1 alpha and IL-6 and acceleration of nitric oxide (NO) and reactive oxygen species (ROS). Immunologically active structures triggered mouse peritoneal MPhis to secrete cytokines and release NO/ROS, even at concentrations as low as 12.5 microg ml(-1). It was found that the O-specific polysaccharide moiety was more immunologically efficient than the glycolipid one, probably due to the position of 3-deoxy-D-manno-octulosonic acid. The results revealed effective structure-immunomodulating relationships of dLPS-derived moieties that are desirable in subcellular anti-cholera vaccine design.