The effect of interleukin 6 (IL-6) on endothelial permeability was examined by measuring fluorescein isothiocyanate-labeled albumin flux across an endothelial cell monolayer. Bovine vascular endothelial cells (BVEC) were cultured up to confluency on collagen-coated polycarbonate micropore filters and then the filters were mounted on modified Boyden chambers. Treatment of the BVEC with IL-6 at 100 ng/ml for 21 h caused a remarkable increase in the permeability of fluorescein isothiocyanate-labeled albumin across the endothelial monolayer. This effect of IL-6 was concentration dependent, in the range from 10-200 ng/ml of IL-6. The effect of IL-6 was also time dependent, the maximal level being reached at 21 h from the beginning of the treatment. This stimulatory effect of IL-6 on albumin clearance was completely abolished by the addition of anti-IL-6 antibody. Light microscopic observation of a cross-section of a monolayer showed that the IL-6-induced increase in the permeability was correlated with changes in cell shape and rearrangement of intracellular actin fibers. IL-6 did not show any cytotoxicity toward or growth inhibition of endothelial cells, even at more than 200 ng/ml. The enhancing effect of IL-6 on the increase in the permeability was reversible; when IL-6 was removed by a medium change and the cells were incubated for a further 24 h without IL-6, the permeability was restored to the control level. These results suggest that IL-6 can induce an increase in endothelial permeability in vitro by rearranging actin filaments and by changing the shape of endothelial cells.