The permeability of the tight junctional system of myelin, at the juxtanodal myelin terminal loops and Schmidt-Lanterman incisures, was investigated using the ionic tracer lanthanum (a) in vivo followed by fixation, (b) concurrently with fixation, (c) following fixation. Employing the same methods the juxtanodal membrane complex formed between myelin loops and axolemma was also tested. The results of this study demonstrate that the periaxonal space (between axon and Schwann cell) is apparently accessible to lanthanum via the myelin loop-axolemmal junction, irrespective of the mode of exposure of myelinated fibres to the tracer. Similarly, the tight junctions between adjacent myelin terminal loops apparently do not prevent lanthanum penetration either in living or in fixed nerves. By contrast the tracer obtained access to the extracellular space within incisures only in vivo. The results are interpreted in terms of the permeability of nodes and incisures in vivo to physiologically important ions and related to current concepts of the electrophysiology of the myelinated nerve fibre.