Nonsyndromic cleft lip with or without cleft palate (CL+/-P) is a congenital orofacial anomaly that derives from an embryopathy with failure of nasal process and palatal shelves fusion. CL+/-P is one of the most common malformations, affecting 1/700-1/1000 live births among Caucasians. Early investigations have suggested that a clefting gene may be located on the short arm of chromosome 6 (6p), as well as in other regions. In this study, we analyzed a large sample of families by using eight PCR markers that map on chromosome region 6p23-p24. The admixture test, as implemented in the HOMOG program, was significant when tested against multipoint data (alpha = 0.60, P value 0.00004); the lod score calculated, assuming heterogeneity, was 3.60 at 1 cM telomeric to D6S259. Taken together these data demonstrate the presence of a locus for CL+/-P in the 6p23 chromosome region.