As indicated when considering Proposal 1, a flow of ~ 0.6 µL g−1 min−1 or more would be required to remove the efflux markers at the observed rate. For a 1400 g brain, that is c. 1.2 L day−1 roughly twice the generally accepted rate of CSF production. Thus even if the rest of this proposal is correct, either the glymphatic flow does not direct ISF out of the brain directly to lymphatic vessels or the rate of CSF production is greater than is generally accepted.