The homing and adhesion of circulating cells to target tissue vasculature precedes their subsequent invasion of inflamed tissue. Polymorphonuclear cells (PMNs), key players in most inflammatory events, are among the first cells to arrive. The present work, performed on CNS lesions from mice with experimental autoimmune encephalomyelitis, provides morphologic evidence for interactions between PMNs and unique, frondlike extensions from endothelial cells (EC) during early attachment. Platelets also were seen attached to these endothelial fronds. The structures projected into vessel lumina from the vicinity of tight junctions and were often branched and complex, the latter characteristics suggesting a possible role in cellular 'trapping'. Polymorphonuclear cells appeared to traverse the CNS vasculature between EC where the blood-brain barrier was severely compromised with junctional complexes reduced to simple contact points. The cells from which the fronds derived were often plump and possessed cytoplasm rich in organelles, perhaps indicative of activation. The present report contrasts with previous observations on lymphocytes in the same system where lymphocytic pseudopodia formed intimate contacts before their burrowing directly through the endothelium and where EC fronds were not involved.