Nuclear pore complexes (NPCs) are among the most versatile cellular channels. These large protein assemblies mediate and control transport between the cytosol and the nucleus. They form a highly selective and, thus, tight nuclear barrier between these compartments. By means of the nuclear barrier, intracellular reactions can take place at separated organelles and the pivotal DNA can be kept out of deleterious material's reach. The tightness of the nuclear barrier is therefore physiologically essential. On the other hand it presents a 'kill-joy' for gene therapy. The latter requires nuclear delivery of large therapeutic cargoes (30-50 nm) which, however, fail to pass the 10 nm wide NPC. It is our ultimate goal to increase the efficiency of gene therapy. Recently, it was shown in oocytes of Xenopus laevis that NPCs dilate from about 82 to 110 nm within min after injection of the glucocorticoid analog dexamethasone (final concentration 60 nM). Dexamethasone induced NPC dilation was receptor-dependent. In the present paper we show that at higher concentrations, 500 nM, dexamethasone induces NPC dilation in a recepetor-independent manner. We analyzed by means of atomic force microscopy the structural details of NPC dilation and correlated them with functional changes in nuclear envelope permeability. 2 min after dexamethasone injection NPC dilation was found at its maximum (approximately 140 nm). In addition, a yet unknown configuration, so-called giant pore, up to 300 nm in diameter, was visualized. Giant pore formation renders the nuclear envelope permeable to a large macromolecule, 77 kDa FITC-dextran (molecule diameter up to 36 nm), which is generally excluded by NPCs. We conclude that dexamethasone transiently opens unspecific pathways for large macromolecules. Dexamethasone treatment could be potentially useful for improving the efficiency of nuclear gene transfection.