Type IV collagen is a complex molecule composed of three alpha chains that can be of types alpha 1(IV) to alpha 5(IV). Each alpha chain contains an amino-terminal collagenous domain and a carboxyl-terminal noncollagenous (NC) domain consisting of 229 amino acids, which is involved in intermolecular cross-linking to construct the basement membrane network. Specific localization of alpha 5(IV) collagen in glomerular basement membranes (GBM) in the kidney indicates its crucial role for that construction. In human kidney cortex and skin RNA, we found an alternative splicing transcript which skips exon 50 of the alpha 5(IV) collagen gene using reverse transcription-polymerase chain reaction and direct sequencing of the PCR products. This alternative splicing introduces a stop codon at the first codon of exon 51, resulting in an mRNA encoding a protein lacking the 84 NC domain carboxylterminal amino acid residues encoded by exons 50 and 51. Recently, gene mutations affecting the alpha 5(IV) collagen NC domain have been reported in patients with X-linked Alport syndrome who display GBM destruction and progressive renal failure, which are usually milder in female patients. Therefore, the alternative splicing, if its truncated products are dominantly expressed in glomeruli, may cause GBM impairment and renal failure progression.