This manuscript presents the design and initial outcomes of the New England Family Study's (NEFS) High-Risk Project, one of the few epidemiologically representative cohorts that has prospectively followed a large sample of offspring of parents with both affective and non-affective psychotic disorders from the fetal period forward. The goals of this report are: (1) to describe in some detail the design, data collection methods, and resulting sample of this project; and (2) to prospectively identify and compare rates of childhood neurological impairments among offspring of psychotic and nonpsychotic parents, with a particular emphasis on offspring risk in relation to specific classes of parental psychosis (i.e., affective vs. non-affective psychosis). The investigators identified a pool of 755 parents with potential psychotic disorders, located over 80% of these and confirmed psychotic diagnoses for 212 affected parents and 132 unaffected control parents. At birth, the 259 offspring of parents with psychosis had approximately a twofold increased risk of abnormal neurological functioning compared to offspring of families with no psychotic history. This was most pronounced among the 58 offspring of parents with schizophrenia. Similar trends were observed at ages 1 and 7 years although these did not reach statistical significance. Neither at birth nor at any of the follow-up assessments were the 157 offspring of parents with affective psychosis found to be at elevated risk of neurological impairment. Implications for future research and potential preventive interventions for at-risk individuals are discussed. © 2013 Wiley Periodicals, Inc.