We have investigated the role of human mesothelium in an in vitro model of peritonitis on the monocyte adherence to and migration across monolayers of peritoneal mesothelial cells. Monocytes adhere avidly to non-activated mesothelial cell monolayers; however, migration in this situation was minimal. Prestimulation of the monolayers with II-1 beta did not alter these results. Anti-CD18 and anti-VLA-4 mAbs used in combination had an additive inhibitory effect on monocytes adherence to resting or IL-1 beta-pretreated mesothelial cells. MCP-1 and TGF-beta are secreted by mesothelial cells. Both have a modest role in mesothelium-induced monocyte chemotaxis: mAbs against these cytokines had an additive inhibitory effect on the chemotaxis induced by supernatant from 24-h prestimulated mesothelial cells. Our results indicate that the mesothelium itself has a limited role in the influx of monocytes into the peritoneal cavity during the onset of peritonitis.