About 80% of the mutations identified to date in the Adenomatous Polyposis Coli (APC) gene have been found in the 5' half of the coding sequence, the vast majority of which (>95%) are nonsense or frameshift mutations that result in the loss of the carboxyl terminus of APC protein. Using a stop codon assay in yeast recently developed by others (Ishioka et al., 1997), we have screened the 5' half of the APC gene for mutations in 7 unrelated families affected with Familial Adenomatous Polyposis. The assay relies on the expression of a yeast reporter gene fused in frame to one of 3 contiguous segments of the APC open reading frame. Here we report on the detection by this assay of 5 germline mutations, 4 of which lie upstream of exon 15, where lesions appear to be sometimes difficult to detect by standard methods.