Oligonucleotides corresponding to conserved sites between the human and mouse amyloid precursor protein (APP) genes have been used to polymerase chain reaction (PCR) amplify and sequence the promoter region of the APP gene from chimpanzee, gorilla, orang-utan, papio and African green monkey. Several novel conserved potentially-regulatory sequences of the APP gene have been detected after alignment of the APP promoter sequences: an apolipoprotein E-B1 (APOE-B1) element at position -450, also present in the APOE gene, two activator protein-2 (AP-2) sites at positions -450 and -301 and an intermediate early-1 gene (IE1) site at position -280. These elements are conserved in all mammalian APP promoter sequences studied. Additionally a previously detected heat shock element (HSE) at position -317, and an activator protein-1 (AP-1) site at position -350 are also conserved. Knowledge of the essential regulatory elements at the APP gene constitute the basis for understanding its transcriptional control and subsequent model studies.