Altered calcium homeostasis is implicated in the pathogenesis of Alzheimer's disease (AD). Much effort has been put into understanding the association between protein mutations causative of this devastating neurodegenerative disease and perturbed calcium signaling. Whereas the presenilin mutations have received most attention in the context of neuronal calcium signaling, we focused on the effects of APP with the so-called Swedish mutation (APPswe) on spontaneous neuronal activity. We observed that primary hippocampal neurons from an APPswe transgenic rat showed increased frequency and unaltered amplitude of spontaneous calcium oscillations as compared to wild-type neurons. We found that the altered calcium signaling of APPswe transgenic neurons was unlikely to be due to modulation of the NMDA or nicotinic neurotransmitter systems, and did not depend on secreted APP derivates. The implications of this effect of APP are discussed.