Seven hundred five cases of agenesis of the corpus callosum (ACC) are reviewed from the literature (n = 660) and from our own observations (n = 45). The diagnosis was made or confirmed using neuroradiological techniques (n = 519) and necropsy or surgery (n = 231). Association with abnormalities often of chromosomes 8, 11, 13-15 and 18 suggests their involvement in abnormal corpus callosum (CC) morphogenesis. Four syndromes (e.g. Aicardi, acrocallosal, Andermann and Shapiro) are characterized by ACC, while others are only sporadically associated (e.g. fetal alcohol syndrome, Dandy-Walker syndrome, Leigh disease, Arnold-Chiari II syndrome). In non-Aicardi patients, the male-to-female ratio was 3:2 and X-linked recessive inheritance is postulated to play a role in some cases. Common abnormalities in acallosal patients included: mental retardation (MR), 73% [corrected]; seizures, 42%; ocular anomalies, 42%; gyral abnormalities, 32%; hydrocephalus, 23%; other central nervous system (CNS) lesions, 29%; costovertebral defects, 24%. Developmental disabilities are not attributable to absence of the CC per se, but due to other CNS malformation or dysfunction, which may be genetic or non-genetic. Future research using recombinant DNA techniques will enable isolation and identification of specific chromosomal defects in those cases with a genetic abnormality.