Gulonolactone treatment of mice resulted in the elevation of hepatic ascorbate and hydrogen peroxide levels accompanied by transient liver swelling and reversible dilatation of endoplasmic reticulum cisternae. Although a decrease in glutathione (reduced form)/total glutathione ratio was observed in microsomes, the redox state of luminal foldases remained unchanged and the signs of endoplasmic reticulum stress were absent. Increased permeability of the microsomal membrane to various compounds of low molecular weight was substantiated. It is assumed that Gulonolactone-dependent luminal hydrogen peroxide formation in the endoplasmic reticulum provokes a temporary increase in non-selective membrane permeability, which results in the dilation of the organelle and in enhanced transmembrane fluxes of small molecules.