Aquaporin 4 (AQP4) is a recently discovered membrane bound water-selective channel and has been described at the light microscopic level to be predominantly expressed in the astrocytes of the brain, especially at the perivascular astrocyte endfoot processes. α1-Syntrophin, a member of dystrophin-associated protein, has also been reported at the light microscopic to be expressed level in the same site of astrocytes as AQP4 and interacts with other molecules through its PDZ domain. AQP4 expression has been reported to be absent at the sarcolemma and the perivascular astrocyte endfoot processes of α1-syntrophin knockout mice. Based on these observations, the molecular association between AQP4 and α1-syntrophin could be speculated. To test this hypothesis, we investigated the ultrasturctural localization of AQP4 and α1-syntrophin in the brain astrocytes by using double immunogold labeled electron microscopy. The results showed that AQP4 and α1-syntrophin colocalized frequently at the astrocyte membrane, especially at the perivascular astrocyte endfoot processes and suggested the presence of linkage between AQP4 and α1-syntrophin at the astrocyte plasma membrane.