Here we report the isolation of cosmid clones containing the whole of the human c-fgr proto-oncogene. We have used these to determine the organization and nucleotide sequence of the exons upstream of exon 4, which have not previously been analysed. We show that, like exons 4 to 12, exon 3 closely resembles its counterpart in the avian c-src and murine lck genes. In contrast, the organization of the upstream exons of c-fgr differs markedly. In particular, the 5' untranslated regions of the c-fgr gene is interrupted by an extra intron. We have also mapped multiple transcriptional start sites within the 5' flanking region of the c-fgr gene and present an analysis of the nucleotide sequences within this region which may be responsible for regulating c-fgr expression.