Cleft lip with or without cleft palate (CL +/- P) is the most frequent craniofacial malformation in different human populations and its cause is largely unknown. Several studies based on population associations have suggested that an allele mapping in the transforming growth factor alpha locus could be responsible, as a risk factor, for the development of the defect. Our investigation of the Taq I polymorphism at the transforming growth factor alpha locus, performed in 40 CL +/- P families, did not find evidence for linkage disequilibrium with particular alleles. Moreover, tight linkage was excluded with the traditional LOD score method.