Chlorpyrifos (CPF) is an organophosphate pesticide widely used in intensive agriculture. Various studies have demonstrated delayed neurotoxic effects in adult mammals after acute CPF exposure. This pesticide induces oxidative stress and neuronal damage, which suggests a possible relationship between CPF exposure and Alzheimers disease (AD). In the present study, we examined in a mice model of AD, long-term changes in the behavior and brain levels of amyloid β after acute CPF exposure. Fifty mg/kg of CPF were subcutaneously injected to Tg2576 (Tg) mice carrying the Swedish amyloid-β protein precursor (AβPP) mutation for AD. General status, body weight, acetyl cholinesterase (AChE) inhibition, and behavioral changes were assessed. Amyloid β fragment (1-40 and 1-42) levels were also measured in the cortical and hippocampal brain regions. A significant and transient decrease in body weight was observed 72 hr after treatment, while no autonomic effects were noted. Motor activity was decreased in Tg mice seven months after CPF treatment. Acquisition learning in a water maze task was not affected, but retention was ameliorated in CPF-exposed Tg mice. Amyloid β levels increased in the brains of treated Tg mice eight months after CPF exposure. The results of this study show that some behavioral changes persisted or emerged months after acute CPF exposure, while amyloid β levels increased. These findings raise concern about the risk of developing neurodegenerative diseases following moderate exposure to CPF in vulnerable subjects.