The aim of this study was to evaluate the effect of self-etching primers on nerve conductance. A self-etching primer (One Up Bond F) which combines etching and bonding in one step, and a fifth-generation bonding agent (Prime&Bond NT) were tested. Isolated rat sciatic nerves were placed between two platinum electrodes in a bath containing Tyrode solution. The bonding agents were brought into contact with the nerves and the evoked compound action potentials (CAP) were recorded before and after contact with the materials. One Up Bond F caused total inhibition of the CAP within an average time of 7 min. All CAPs in this group were blocked irreversibly. As with Prime&Bond NT, the reduction in CAP was 45.9% after an application time of 15 min, after which readings were terminated. Recovery of the CAP in this group were maintained after rinsing with fresh tyrode solution. One Up Bond F elicited faster blocking of nerve conductance under the conditions of this model. In the context of dentin desensitization with bonding agents, the self-etching primer may be more effective, clinically.