BRCA1 is a tumour suppressor gene located on chromosome band 17q21. It is estimated that mutations in the BRCA1 gene account for approximately 45% of the breast cancer families and almost all of the breast/ovarian cancer families. We have used single strand conformation polymorphism analysis, direct sequencing, allele specific oligonucleotide hybridisation, and reverse transcription polymerase chain reaction (RT-PCR) to look for mutations in the BRCA1 gene in 49 breast or breast/ovarian cancer families. Five distinct mutations, three novel and two previously observed, were detected in seven families. Each novel mutation was identified in one family: 3896delT in exon 11, a splicing mutation in the intron 9-exon 10 junction, and an inferred regulatory mutation. The 185delAG in exon 2 was found in three families sharing the same haplotype, but this haplotype is different from that shared by the Ashkenazi Jewish families, suggesting that the 185delAG in our families may have arisen independently. Another previously reported mutation, the 3875del4 in exon 11, was identified in one family. Of the 49 families examined, linkage analyses for both the BRCA1 and the BRCA2 regions were performed on 33 families, and mutations in the BRCA1 gene were identified in all but one family that have a lod score above 0.8 for BRCA1. All of the mutations cause either a truncated BRCA1, or loss of a BRCA1 transcript, thus are likely to be functionally disruptive. In addition, we found that alternative splicing is a common phenomenon in the processing of the BRCA1 gene. Seven variant BRCA1 transcripts were identified by RT-PCR; all but one maintained the BRCA1 open reading frame. We believe that alternative splicing may play a significant role in modulating the physiological function of BRCA1.