Potential recordings and potential clamp of isolated myelinated fibers from the sciatic nerve of acutely uremic rats showed a marked decrease in excitability related to a decrease in the specific Na permeability (P Na) of the nodal membrane. Mean value of the available P Na in the resting node of the uremic rats was 24% of the P Na in a control group. This change explained the decreased nerve conduction velocity in the acutely uremic rat. The Na current reversal potential was decreased in some fibers, reflecting an axoplasmic Na accumulation. The decrease in P Na was to a large extent caused by an increased inactivation, due to a negative shift (about 10 mV) of the steady state inactivation curve along the potential axis. The activation of P Na was similarly shifted (about 10 mV) to a more negative potential region. Such changes may be caused by elevated intracellular [Ca], suggesting a disturbance in Ca metabolism or an intracellular accumulation of cationic metabolites (which possibly have a similar effect) in rats with acute uremia.