1. Alloxan and its auto-oxidation product hydrogen peroxide (H2O2) irreversibly depolarize insulinoma cells by opening a non-selective cation channel. The channel opened is characterized by a linear current-voltage relation with a conductance of approximately 70 pS and very slow kinetics (of the order of seconds). 2. Cells are protected against the alloxan-induced channel opening and consequent cell depolarization by the presence of H2O2 and hydroxyl radical scavengers. 3. The free radical-activated non-selective cation channel is not operative in isolated patches but can be activated by the application of beta-NAD+ to the cytoplasmic aspect of the membrane.