In childhood, widening of Virchow-Robin spaces is rarely secondary to specific progressive disorders, but more often appears in poorly characterized developmental conditions. From data collected in a neuropediatric department, we examined whether clinical data associated with "constitutional widening of Virchow-Robin spaces" allowed delineation of recognizable entities. Signs in 10 patients, mostly boys, suggested nonspecific cerebral dysfunctions, e.g., developmental delay, nonspecific epilepsy, headaches, or benign macrocephaly. Spaces were sometimes round, subsequently mimicking microcystic malacic lesions. In two patients, abnormal magnetic resonance imaging signals were evident in white matter contiguous to widened perivascular spaces, suggesting a broader disorder of fluid exchanges. Four cases occurred in two sibships. In two families, other patients exhibited early developmental difficulties. Long-term clinical and magnetic resonance imaging surveillance will clarify which cases of primary Virchow-Robin space dilatation imply a benign prognosis. Performance of magnetic resonance imaging on any relative exhibiting minor neuropsychologic handicaps would permit estimations of real genetic incidence.