OBJECTIVE: To study the effects of antipsychotic withdrawal in elderly nursing home residents. DESIGN: Longitudinal prospective study. SETTING: 12 community nursing homes that participated in a randomized controlled trial of an educational program designed to reduce antipsychotic use. SUBJECTS: 271 residents receiving antipsychotics at baseline and remaining in the home for approximately 6 months thereafter. These were placed into two groups: those with continued use of antipsychotics at follow-up (n = 207) and those with drug discontinued (n = 64). MEASUREMENTS: Change between baseline and follow-up for several standard measurements. These included behavior problems, as reported by both regular care providers (Nursing Home Behavior Problem Scale) or a blinded study rater (items from the Brief Psychiatric Rating Scale), observer-rated psychiatric symptoms (subset of the Brief Psychiatric Rating Scale), and other standard tests of function (Activities of Daily Living, Mini-Mental State Examination, Geriatric Depression Scale, and Abnormal Involuntary Movements Scale). RESULTS: The frequency of behavior problems did not increase in residents with antipsychotics discontinued. For these residents, observer-rated psychiatric symptoms decreased by 21% (P = 0.003), which resulted from a 27% decrease in adverse affective symptoms (P = 0.0002). Residents with drug discontinued had no deterioration in any of the measures of function. CONCLUSION: In this sample, nursing home residents whose antipsychotics were discontinued had significantly improved affect and no discernable adverse effects.