This study was designed to determine the ACTH-corticosterone response to two types of stress in relation to the daily rhythm of food and water intake in the iron-deficient rat. Rats were fed diets containing 2, 10 or 50 mg iron/kg diet between weaning at 21 days and the stress experiments at 38 or 42 days of age. The two iron-deficient diets (2 and 10 mg iron/kg) resulted in mean hemoglobin concentrations of about 6.0 and 8.5 g/dl, respectively, in contrast to about 12.5 g/dl in the control group receiving 50 mg iron/kg diet. Food and water consumption followed the normal nocturnal pattern, irrespective of iron intake. ACTH and corticosterone showed the normal baseline peaks at the 2000 hour lights-out point in all groups. Responses to handling and placement into another cage were similar in most respects but suggested an inappropriately low corticosterone response despite high ACTH values only at the 2000 hour point. However, there was no evidence of similar differences in response to the more potent stress of an i.p. injection of histamine 1 mg/100 g body weight. In contrast to the reports of more clear-cut effects of iron deficiency on norepinephrine, the changes in ACTH and corticosterone response to stress seem relatively modest.