A male infant is described showing all the major features of the oral-facial-digital syndrome (OFD): lobulated tongue with hypertrophic frena, fibrous bands extending into alveolar clefts, pseudocleft of upper lip, cleft palate, hypoplastic alae nasi, dystopia canthorum, various digital anomalies, and typical X-ray appearance of the skull. A partial agenesis of the corpus callosum with a lipoma was indicated by pneumoencephalography and angiography. The OFD syndrome is confined to females. In the present case an XXY chromosome constitution was demonstrated by cytogenetic studies. The occurrence of OFD and Klinefelter's syndrome in one and the same person is ascribed to a very rare coincidence. OFD is considered to be due to an X-linked dominant mutant gene, with a recessive lethal effect. X-linkage is supported by the pattern of a more extreme lethal expression in hemizygous males versus viability of heterozygous females. An XXY individual is viable, presumably because of the normal allele which is active in a fraction of its cells. Other reports of males with OFD are critically evaluated.