Streptozotocin, which is a naturally occurring nitrosoamide used extensively to produce diabetes mellitus in experimental animals, has been known to be chemically stable only under acidic condition (pH 4). The present study was conducted to determine whether its degradation products formed under various conditions can induce hyperglycemia in female rats. Streptozotocin in phosphate buffer saline (pH 7.4) resulted in spontaneous degradation rapidly. Furthermore, streptozotocin incubated with plasma isolated from rats was degraded even faster than those in neutral buffer. When streptozotocin was administered iv to rats, significant elevations in blood glucose level were observed within 24 hours. However, rats treated with equimolar concentration of streptozotocin degradation products under the phosphate buffer saline as well as the plasma did not lead to hyperglycemia. These results suggest that, when streptozotocin administered undergo spontaneous breakdown in vivo, its degradation Products do not induce the hyperglycemia in rats.