P73 is located on chromosome 1p36, a region that is frequently deleted in neuroblastoma and other tumors. P73 has been postulated to be a candidate tumor suppressor and imprinted gene that shares significant homology with the p53 gene. To investigate the pattern of inactivation of this gene in human non-small cell lung cancers, we studied the six NSCLC cell lines to identify abnormal methylation in exon 1 and the allelic expression using StyI polymorphism analysis. We also examined the p73 gene expression in these six cell lines by reverse transcription-PCR as well as the expression of p73 protein in the five cell lines inducing tumors by immunohistochemistry. Homozygous allelic expression was demonstrated in all six cell lines and the GC/GC genotype was the predominant type. P73 was aberrantly methylated in all these six lung cancer cell lines. Complete loss of the p73 expression both at mRNA and the protein level was associated with the p73 methylation. Our results show that methylation of the p73 gene could be an important mechanism in silencing expression of this gene in human non-small cell lung cancers.