Whether social isolation of adult rats under standard laboratory conditions produces significant long-term alterations in behavior and physiology is unclear. In the present study, male Sprague-Dawley rats were singly or paired-housed for 10 wk. During this period, they were tested for acquisition, extinction, and reacquisition of heroin (0.3 mg/kg)-conditioned place preference. Fecal corticoid metabolite levels were analyzed several times throughout the period of housing, and food consumption and body weight were monitored. During place conditioning, heroin induced a significant increase in locomotor activity in both singly and pair housed rats, and the resulting place preference was similar in both groups. However, singly housed rats showed increased motor reactivity to heroin on reconditioning after extinction and displayed significant reacquisition of conditioned place preference, compared with pair-housed animals. Over the 10-wk period of the study, there were no differences in body weight or food consumption between groups. Mild significant increases in relative adrenal gland weight and decreases in relative brain weight were noted in singly housed animals compared with those paired. Significant decreases in nocturnal fecal corticoid metabolite output were noted in both groups, with loss of circadian variation in fecal corticoid levels over the course of the study. These data suggest that male Sprague-Dawley rats, irrespective of single or pair housing, develop reduced hypothalamic-pituitary-adrenal axis activity over time under standard laboratory housing conditions. Single housing can enhance both this effect and sensitivity to the stimulatory and rewarding actions of heroin after withdrawal.