Adenylate cyclase from the bovine cerebral cortex has been solubilized with the nonionic detergent Triton X-100. The physical properties of the enzyme have been determined. These are: sedimentation coefficient, 8.1 S; Stokes radius, 70 A; partial specific volume, 0.79 ml/g; mass, 305,000 daltons; f/f0 1.5. The high partial specific volume measured in the presence of detergent indicates that the enzyme binds a large quantity of detergent (0.28mg of Triton X-100/mg of protein). The mass of the enzyme protein alone is 220,000 daltons. The size and detergent-binding properties of adenylate cyclase from bovine cerebral cortex are different from those previously reported for adenylate cyclase from the rat renal medulla (Neer, E. J. (1974) J. Biol. Chem. 249, 6527-6531). The renal enzyme is smaller by 60,000 daltons than the cerebral enzyme and does not bind measurable amounts of detergent. The amount of detergent bound by cerebral adenylate cyclase is characteristic of intrinsic membrane proteins. It suggests that there is a hydrophobic region on the surface of the molecule by which it is held in the plasma membrane.