Human umbilical vein endothelial cells cultured on a collagen lattice were used to study the effects of the interaction between human monocytes and endothelial cells on endothelial von Willebrand Factor (vWF) release and prostacyclin (PGI2) production by these cells. The effects of monocytes were compared with those of other leucocytes, conditioned media from monocytes, and agonists such as interleukin 1 (IL-1) and the phorbol ester PMA. Because the cell culture system used allows simultaneous analysis of the lumenal and ablumenal compartment of endothelial cell monolayers, we also studied into which direction these products were released by endothelial cells. Under quiescent conditions the concentration of vWF in the ablumenal compartment was about three-fold higher than that in the lumenal compartment, whereas PGI2 was equally distributed between the two compartments. Direct cell-cell contact between purified monocytes and endothelial cells strongly enhanced both vWF release and PGI2 synthesis, in a dose-dependent and monocyte-specific manner. The monocyte-induced enhancement of PGI2 production, however, was much earlier in onset than that of vWF. Secretory products from monocytes also enhanced endothelial PGI2 synthesis, although to a lesser extent than with monocytes that were in direct contact with endothelial cells. In contrast, the monocyte-induced enhancement of endothelial vWF release was completely dependent on the direct interaction between monocytes and endothelial cells.