The effect that bath application of sulphydryl reagents (SR) exerts on frog sartorius motor endplate sensitivity to iontophoretically applied carbachol (CCh) has been studied. Sensitivity to CCh is expressed as the ratio of the CCh potential (mV) to the nanocoulombs delivered by the iontophoretic pulse and has been determined before and after addition of SR to the bath. Two groups of SR have been tested: oxidizing reagents, o-iodosobenzoate and reducing agents, dithiothreitol (DTT). CCh was applied iontophoretically by means of a microelectrophoretic programmer with constant current source. Exposure of the muscle to 1 mM DTT in a bath pH range of 7-8 for 2 to 85 min showed no significant differences in endplate sensitivity to CCh before and after addition of the reducing agent. o-Iodosobenzoate at a 1 mM bath concentration (pH 7) for 2 to 19 min strongly decreases endplate sensitivity to CCh. The statistical methods used were Wilcoxon rank tests and linear regression. Since previous studies have shown that oxidizing and reducing SR evoke depolarizations when applied iontophoretically at the endplate region, these results suggest that activation of the receptor is achieved only when SR are delivered iontophoretically, and that discrepancies observed can be attributed mainly to the different techniques of drug application.