Recently, an association of a specific transforming growth factor alpha (TGFA) haplotype has been reported to occur in patients with nonsyndromic cleft lip and palate (CLP) who had a positive family history of the disorder. We tested linkage of CLP to TGFA in 12 multiplex families with clefting. TGFA haplotypes were constructed on the basis of three polymorphic restriction sites. No haplotype was associated with CLP, and discordant inheritance of TGFA haplotypes was observed in a single informative family. The log odds (LOD) score was -2.1 at theta = .05. These findings indicate that CLP and TGFA are not tightly linked in these families.