A useful first step in any chemical characterization of the sodium channels in nerve membrane would clearly be the identification of some measurable property of the channel that does not depend on the intactness of the tissue. To this end, tetrodotoxin and saxitoxin, which bind specifically to sodium channels, have been tritiated and their binding to rabbit, lobster and garfish non-myelinated nerve fibres examined. In each case, a component of the binding curve was found that saturated at concen trations of a few nanomolar. In addition, non-specific binding, indicated by a linear dependence of the amount bound on concentration, occurred. A solubilized membrane preparation from garfish nerve shows the same specific binding component as that of the intact nerve. The saturable component of binding seems to reflect the sodium channel density in nerve, and this is extremely small, being about 27/m 2 in the rabbit nerve and as small as 6/jtfjtm 2 in the garfish nerve.