The adenosine analogue formycin A was recently introduced as a potent insulin secretagogue in normal pancreatic islet cells. In the present study, formycin A was found to inhibit insulin release and to exert a cytotoxic effect in tumor islet cells of the RINm5F line. The latter effect was concentration-related in the 10-100 microM range of formycin A concentrations, not rapidly reversed, and not reproduced by adenosine. This study thus reveals that formycin A may display cytotoxic potential in the same range of concentrations in which it causes a progressive increase of glucose-stimulated insulin secretion in normal pancreatic islets.