Autoimmune encephalitis is increasingly recognized in patients with otherwise unexplained temporal lobe epilepsy. In particular, patients with encephalitis associated with autoantibodies against NMDA receptors present with epilepsy, memory deficits and psychiatric symptoms. In order to investigate the pathophysiology of this disease we stereotactically injected anti-NMDA receptor-antibodies bilaterally into the dentate gyrus of adult female rats. In rats injected with these antibodies we found a massive impairment of long-term potentiation (LTP) compared to saline-injected rats. This was accompanied by an impaired learning behavior in the Morris water maze hidden platform task. Moreover, stereotactic injection of cerebrospinal fluid (CSF) from patients with anti-NMDA receptor encephalitis also resulted in a reduction of dentate gyrus LTP. Control rats injected with CSF from epilepsy patients without anti-NMDA receptor autoantibodies showed LTP which was lower than in saline-injected rats but significantly higher than in animals treated with anti-NMDA receptor-antibodies. Intracellular recordings of dentate gyrus granule cells showed that NMDA receptor-mediated excitatory postsynaptic potentials were significantly reduced in rats treated with anti-NMDA receptor-antibodies. These results suggest that anti-NMDA receptor antibodies lead to reduced NMDA receptor function which could explain the memory impairment found in patients with anti-NMDA receptor encephalitis.