Permeability of cerebromicrovascular endothelium has been investigated in a new model of cultured cells. The endothelial cells are grown on dextran microcarriers and constitute a barrier for trypan blue (TB) binding to the dextran beads. Changes in the permeability of microcarrier-cultured endothelium have been investigated during the exposure of cells to arachidonic acid or substances involved either in arachidonate metabolism or stimulation of cAMP. The results demonstrate enhanced TB passage through the endothelial barrier during exposure to high concentrations of arachidonic acid and indomethacin, but not to ibuprofen. The effect of indomethacin could be prevented by pretreatment with dexamethasone. Dexamethasone alone did not influence the barrier. Forskolin, a drug which stimulates the catalytic unit of adenylate cyclase, did not affect the endothelial permeability to TB. These findings support the contention that substances derived from a disturbed cellular membrane contribute to the altered blood-brain barrier function found under pathological conditions.