There is provided a series of oxime-containing macrocyclic acyl guanidines of Formula (I) or a stereoisomer; or a pharmaceutically acceptable salt thereof ##STR00001## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, n and X as defined herein, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein (APP) by .beta.-secretase and, more specifically, inhibit the production of A.beta.-peptide. The present disclosure is directed to compounds useful in the treatment of neurological disorders related to .beta.-amyloid production, such as Alzheimer's disease and other conditions affected by anti-amyloid activity.