1. Whole-cell voltage-clamp recordings were used to study the characteristics of a non-selective cation current, activated by intracellular ß-NAD+, present in CRI-G1 insulin-secreting cells. The monovalent cations Na+, K+ and Cs+ were equally permeant through this channel. 2. The magnitude of the ß-NAD+ current was dependent on the concentration of both ß-NAD+ and Ca2+ in the cell. The properties of the ß-NAD+-activated macroscopic current are similar to those of the ß-NAD+-activated non-selective cation channel (NSNAD) examined at the single channel level in this cell line. 3. The presence of intracellular reduced glutathione (GSH) inhibited the ß-NAD+-activated macroscopic current and the activity of the NSNAD channel in inside-out patch recordings. 4. The inhibition of ß-NAD+-activated currents by GSH is mimicked by its analogue ophthalmic acid but not by another thiol reducing agent dithiothreitol, indicating the presence of a specific GSH binding site present on the NSNAD channel or associated protein.