It is common among Israeli Arabs who live in the villages to prefer consanguineous marriages, particularly among first cousins. In addition, such villages are populated by a few (less than 20) original families, and inter-family/inter-village marriages are infrequent. The purpose of this study was to examine the consequences of such "consanguinity" in Taibe, a large Arab village, 30 km from Tel Aviv. Six hundred ten families were prospectively ascertained through infants who were routinely seen in the local "Well Baby Clinics." A significant increase in the incidence of major malformations was noted in relation to the closeness of the parental relationship. For the index cases group the prevalence of individuals with major malformations were 5.8% in the product of inter-village marriages, 8.3% in the intra-village non-related matings, 15.1% in the distant consanguineous group, and up to 15.8% in the progeny of first-cousin marriages (P less than 0.001). In the siblings of these index cases, the frequency of major malformations was 4.3%, 4.5%, 10.5%, and 10.3%, respectively. Analysis of the major malformations by each body system showed the same trend. The study demonstrates a marked high rate of consanguineous marriages, whose effect leads to a marked increase in major malformations and thus a prominent public health problem in such villages. This requires a unique genetic counseling approach.