OBJECTIVES: To examine affect and physiological stress in frail older adults in response to a voluntary nursing home relocation. DESIGN: Randomized, controlled trial. SETTING: Long-term care facility located within the greater Philadelphia, Pennsylvania, community. PARTICIPANTS: Seventy-seven nursing home residents, aged 65 and over. INTERVENTION: Experimental group residents were relocated to a newly built nursing home facility with a cluster design in the fall of 2001; control group residents were moved after study completion in the spring of 2002. MEASUREMENTS: Mini-Mental State Examination scores, Observed Affect Rating Scale scores, salivary cortisol, blood pressure, and pulse obtained 1 week before moving and 1 week and 4 weeks after moving. RESULTS: Relocated nursing home residents demonstrated significant differences in salivary cortisol and mood from a randomly selected group of residents that had not yet moved. Relocation resulted in significantly higher cortisol levels 1 week after the move (P=.005), followed by a significant decline in afternoon cortisol at 4 weeks after the move (P=.03). Moreover, relocated residents had significantly lower depression and anxiety symptoms and pulse rates than residents who had not yet moved. CONCLUSION: These findings have important implications for planning medical and social services for relocated elderly. Efforts should be made to prepare individuals for the initial stressors associated with relocation, but it also appears that the stress imposed by relocation is time limited and may begin to ease as early as 4 weeks postmove.