Isolated rat liver gap junctions were treated with two non denaturant detergents, digitonin and octyl glucoside. The structural changes of the gap junctions were observed by electron microscopy (thin sections and freeze-fracture). Octyl glucoside alone was inefficient in modifying gap junction structure. Digitonin induced a partial spacing of the two adjacent junctional membranes. The combined action of the two detergents resulted in a complete disorganization of the particle network normally seen in freeze-fracture and of the pentalaminar sheet seen in thin sections. This disappearance of the junction structure suggests that the inter-subunits bonds have been disrupted.