The spatial specificity and stability of subplasmalemmal domains of high-polarized mitochondria (Delta Psi m(HIGH)) in human oocytes and cleavage stage embryos were investigated in instances where changes in pericortical/subplasmalemmal organization resulted in the corresponding cytoplasm becoming translucent and largely devoid of mitochondria, either by experimental manipulation or as a result of spontaneous, stage-specific morphodynamic processes. The developmental significance of high-polarized mitochondria was examined in early embryos where their loss from a cell(s) occurred by elimination into a focal cluster of small extracellular fragments, or by disproportionate segregation between blastomeres. The findings demonstrate that pronounced changes in the organization of the pericortical and subplasmalemmal cytoplasm do not affect these domains, and their displacement under experimental conditions is fully reversible. By contrast, in instances of their significant or complete elimination, the domains of high-polarized mitochondria did not reform and the affected cell(s) remained intact and undivided during culture. The findings (i) support a spatial specificity and stability for high-polarized mitochondria, which in human oocytes and early embryos, represent a very small fraction of the total mitochondrial complement, and (ii) are discussed with respect to their suggested participation in transmembrane and signal transduction processes. It is proposed that Delta Psi(HIGH) mitochondria located in subplasmalemmal domains are 'vanguard' organelles that can sense and respond to regulatory signals of extrinsic and intrinsic origin during early development.