We examined the effect of a single STZ administration on subsequent islet isograft and allograft survival in NOD mice. Young prediabetic NOD mice were rendered diabetic by STZ administration and transplanted with islet isografts 8-11 days later. The earliest loss of islet function occurred on postgraft day 49. In sharp contrast, 15 of 16 isografts in spontaneously diabetic mice were destroyed within 17 days postgrafting. A comparison of the age of islet isograft destruction in STZ-induced diabetic NOD mice with the course of diabetes development in the NOD mouse colony clearly showed that STZ administration at the prediabetic stage led to a significant delay of diabetes onset in isografts. When STZ was given to overtly diabetic NOD mice, both islet isografts and allografts survived significantly longer than those in untreated, spontaneously diabetic NOD mice. However, the degree of prolongation induced by STZ was much smaller compared with that induced by ALS, a potent immunosuppressive reagent. In vitro mixed lymphocyte culture experiments showed that spleen cells of mice given STZ exhibited time-dependent reduction of their alloantigen reactivities. These results demonstrate that STZ, which is commonly used to induce diabetes in various experimental animals, also possesses an immunosuppressive property, although it is relatively weak compared with ALS.