The present study tested the hypothesis whether a histamine dependent pathway is involved in leukocyte-endothel interaction in the early phase of bacterial meningitis. Using confocal laser scanning microscopy we investigated leukocyte rolling in brain venules in vivo during 4 h in experimental pneumococcal meningitis in the rat. Leukocyte rolling, but not firm adhesion induced by intracisternally (i.c.) injected pneumococcal cell wall components, was temporarily inhibited (2 h, 5.6 +/- 1.9 vs. 2.3 +/- 0.9; 3 h, 7.4 +/- 2.7 vs. 3.1 +/- 1.3/100 microm/min) by diphenhydramine, a histamine H1 receptor antagonist. Histamine, possibly released by activated mast cells, is known to initiate P-selectin upregulation and subsequent leukocyte rolling. This data suggest that histamine is a mediator of leukocyte rolling in the early phase of bacterial meningitis.