Background Increasing evidence suggests that seizures and status epilepticus can be immune-mediated. We aimed to describe the clinical features of a new epileptic disorder, and to establish the target antigen and the effects of patients' antibodies on neuronal cultures. Methods In this observational study, we selected serum and CSF samples for antigen characterisation from 140 patients with encephalitis, seizures or status epilepticus, and antibodies to unknown neuropil antigens. The samples were obtained from worldwide referrals of patients with disorders suspected to be autoimmune between April 28, 2006, and April 25, 2013. We used samples from 75 healthy individuals and 416 patients with a range of neurological diseases as controls. We assessed the samples using immunoprecipitation, mass spectrometry, cell-based assay, and analysis of antibody effects in cultured rat hippocampal neurons with confocal microscopy. Findings Neuronal cell-membrane immunoprecipitation with serum of two index patients revealed GABA(A) receptor sequences. Cell-based assay with HEK293 expressing alpha 1/beta 3 subunits of the GABA(A) receptor showed high litre serum antibodies (>1:160) and CSF antibodies in six patients. All six patients (age 3-63 years, median 22 years; five male patients) developed refractory status epilepticus or epilepsia partialis continua along with extensive cortical-subcorfical MRI abnormalities; four patients needed pharmacologically induced coma. 12 of 416 control patients with other diseases, but none of the healthy controls, had low-titre GABA(A) receptor antibodies detectable in only serum samples, five of them also had GAD-65 antibodies. These 12 patients (age 2-74 years, median 26.5 years; seven male patients) developed a broader spectrum of symptoms probably indicative of coexisting autoimmune disorders: six had encephalitis with seizures (one with status epilepticus needing pharmacologically induced coma; one with epilepsia partialis continua), four had stiff-person syndrome (one with seizures and limbic involvement), and two had opsoclonusmyoclonus. Overall, 12 of 15 patients for whom treatment and outcome were assessable had full (three patients) or partial (nine patients) response to immunotherapy or symptomatic treatment, and three died. Patients' antibodies caused a selective reduction of GABA(A) receptor dusters at synapses, but not along dendrites, without altering NMDA receptors and gephyrin (a protein that anchors the GABA(A) receptor). Interpretation High titres of serum and CSF GABA(A) receptor antibodies are associated with a severe form of encephalitis with seizures, refractory status epilepticus, or both. The antibodies cause a selective reduction of synaptic GABA(A) receptors. The disorder often occurs with GABAergic and other coexisting autoimmune disorders and is potentially treatable.