The effects of x-irradiation on the subcellular structure of the human urinary bladder were investigated by electron microscopic examination of biopsies taken during check cystoscopies from 25 patients between 1 month and 22 years after completion of a course of therapeutic radiation. All tissues of the bladder wall were damaged to some extent by the treatment. In the urothelium this was reflected by the development of more than the usual numbers of lysosomes and autophagic vacuoles in all cell layers. In the bladder wall, large often binucleate or multinucleate fibroblasts were prominent and persistent in all specimens and were associated with the development of progressive fibrosis. The vasculature and the muscle coats of the bladder wall were also damaged. In the blood vessels many endothelial cells were oedematous or necrotic and some intravascular coagulation was also observed. Smooth muscle cells became oedematous soon after irradiation, and after longer time intervals there was focal death and loss of individual muscle cells. The observed degeneration and extensive necrosis of the bladder wall, which involved severe destruction and disorganization of the muscular layers, is sufficient to explain the clinical sequelae of bladder irradiation, namely loss of elasticity, reduced capacity and incomplete micturition with residual urine.