Alloxan-diabetic male rats were used to test effects of pinealectomy (PX) and of sham-pinealectomy (SPX) on blood glucose levels at mid-dark in the daily light-dark (LD 12: 12) cycle. Animals received a diabetogenic dose of alloxan 10 days postoperatively. Blood glucose was measured on days -1, 1, 2, 3, 4, 5, 7, 10 and 15 after 8-hour fasts. Pinealectomized (PX) and non-operated (C) animals were equivalent in their hyperglycemia following alloxan. SPX animals contrastingly showed significantly less response to alloxan than did animals of the other two groups. This difference of the SPX animals was in terms of lower hyperglycemia, better maintenance of body weight and of survival. It is concluded that intracranial surgery alone (SPX) and without visible brain damage can affect mechanisms of glucose homeostasis, and that at least in some circumstances such a surgical effect is not only different from effects of surgical pinealectomy (PX), but is also probably not pineal-dependent. 1 This work was supported in part by a fellowship (K.C.G.) from the University of Wisconsin, Madison, School of Graduate Studies, and research grants (W.B.Q.) from the National Institute of Mental Health (MH-25091), the National Institute of Health (HD-03352, HD-10263, 5-T01-HD-00104-10), USPHS, the Ford Foundation (#630-0505 B, C) and the National Science Foundation (PCM 76-09953).