Glucose‐stimulated (pro)insulin biosynthesis is markedly inhibited is mouse pancreatic islets incubated with micromolar concentrations of 2‐5A ‘core’, (A2'p5'A2'p5'A). Total protein synthesis was also reduced, but to a lesser extent, while insulin release and total insulin content of the islets was untouched by 2‐5A ‘core’. Evidence is given for the presence of a 2‐5A‐dependent endoribonuclease which mediates these effects.