This article presents a new interview-based research instrument for assessing schizotypal symptoms and signs. The Structured Interview for Schizotypy (SIS), which was developed from experience gained in a large, controlled family study of schizophrenia in the west of Ireland and has been field-tested in three other locations, differs from previously available interviews in that it includes: (1) built-in contextual assessments of the pathological nature of certain symptoms (e.g., suspiciousness or ideas of reference); (2) multiple independently scored items, most with closed response options, per symptom scale; (3) extensive assessment of schizotypal signs; (4) symptom probes designed to make responding positively appear nondeviant; and (5) coverage of potentially relevant symptoms and signs not required in current criteria for schizotypal personality disorder. Schizotypal symptoms can be assessed with high reliability by the SIS. When sufficient variability is present, schizotypal signs are also reliably assessed by the SIS, although the reliability is generally lower than that found for symptoms. In three independent pilot studies, schizotypal symptoms and signs assessed by the SIS appear to discriminate significantly the relatives of schizophrenic patients from relatives of controls.