The literature regarding enkephalin transport through the brain endothelial wall,i.e. the blood-brain barrier (BBB), is conflicting. For example, some studies indicate that enkephalins traverse the BBB at low rates similar to other putative neurotransmitters, while other investigations have indicated that enkephalins readily cross the BBB. In addition, it is possible that enkephalins, like other peptides, such as insulin, do not cross the BBB but actively bind to specific peptide receptors on the luminal side of the BBB. Therefore, the present studies were undertaken with freshly isolated bovine brain cor- tical capillaries to determine if [tyrosyl-3H]leucine enkephalin is either specifically bound or taken up by the cell which comprises the BBB in vivo. Brain capillaries were incubated with radiochemically pure [tyrosyl-3H]leucine enkephalin and [l4C]sucrose, an extracellular space marker, at 22–23 C. The amount of 3H radioactivity associatd with brain endothelia increased with time and reached equilibri...