Mutations in the COL4A5 gene encoding the alpha 5 chain of type IV collagen have been found in linkage with X-chromosomal Alport syndrome (AS). To identify COL4A5 mutations in patients from Germany with clinically defined AS, DNA from 20 unrelated patients was analyzed by conventional Southern blotting. By using full length alpha 5(IV) cDNA probes, large COL4A5 deletions could be detected in two patients. In one case, a 34 kb deletion affecting the 14 most 3' exons of the gene was observed. The second patient harbored a complete COL4A5 deletion. In both cases, functional alpha 5(IV) mRNA was unlikely to be present. Clinically, both patients developed end-stage renal failure before age 30. Furthermore, they had characteristic retinal flecks, and sensorineural hearing loss with typical changes on the audiogram. The patient with the complete deletion of COL4A5 lost the renal allograft due to an anti-GBM mediated glomerulonephritis.