Endophenotypes is one emerging strategy in schizophrenia research that is being used to identify the functional importance of genetically transmitted, brain-based deficits present in this disease. Currently, event-related potentials (ERPs) are timely used in this search. Several ERPs, including N400, present deficits in relation to schizophrenia. In order to assess the genetic liability of N400 as a possible endophenotype, a picture semantic matching task (congruent and incongruent pairs of pictures) was performed by 21 unaffected first-degree relatives of patients with schizophrenia, 21 DSM-IV diagnosed schizophrenia probands, and 21 control subjects, matched by age, gender and educational level. Probands and relatives were selected form Multiplex schizophrenia families. Significantly reduced N400 amplitude for congruent categories in N400 was found in probands and relatives in relation to controls. The latency onset and the maximum peak latency of N400 were delayed in both, relatives and probands groups compared to control. The voltage maps of incongruous-minus-congruous difference indicate a more reduced right restricted negativity in probands and relatives, when compared to a widely extended bilateral negativity in controls. No general differences were found between patients and relatives. These results demonstrate an electrophysiological deficit in semantic match processing in clinically unaffected first-degree relatives of patients with schizophrenia, suggesting a possible use of this marker as endophenotype.