Bladder dysfunction occurs after radiation therapy for pelvic malignancies (1) where normal bladder tissue is unavoidably irradiated causing urinary tract symptoms including urgency, frequency and incontinence, adversely affecting quality of life. Understanding the mechanisms underpinning radiation bladder dysfunction is important to achieve maximum tumour kill with minimal normal tissue damage. The purpose of the present study was to examine the effect of radiation on spontaneous contractility or neurogenic-evoked contractions in bladder strips. Bladders strips from male guinea-pigs (250-300g) killed by cervical dislocation under UK Schedule 1 regulations and local ethical approval were prepared as: (1) full thickness (mucosa and detrusor) or (2) detrusor-only (mucosa-free) from the body and trigone regions. Strips received sham or 20Gy irradiation and were studied with in vitro tension recordings. Electrical field stimulation generated neurogenic contractions (0.3ms pulse width, 70V, 10s duration, 0.5, 1, 2, 4, 8 and 16 Hz). Spontaneous contractions were measured as force integral (area under curve, AUC, g.min) and neurogenic contractions as amplitude (g). Data are expressed as mean ± S.E.M. with N and n referring to number of animals and number of strip preparations respectively. Unpaired t-tests were used with p<0.05 considered as significant. Spontaneous contractions in full thickness strips from bladder body were significantly reduced by radiation (N=15, n=19, p<0.05) whereas detrusor-only strips were not affected (N=14, n=19, p>0.05). Trigone strips exhibited low-amplitude changes in baseline tension; activity in full thickness strips was not affected by radiation (N=10, n=15 p>0.05) whereas it was significantly reduced in detrusor-only strips (N=8, n=13, p<0.05). Neurogenic contractions in full thickness strips from bladder body were significantly reduced by radiation at all frequencies tested (N=7, n=11, 0<0.05) whereas detrusor-only strips were not affected (N=6, n=8, p>0.05). The opposite was found in trigonal strips where radiation did not affect neurogenic contractions in full thickness strips (N=7, n=8, p>0.05) but significantly reduced those from detrusor-only strips (N=7, n=9, p<0.05). Radiation-generated differences in neurogenic contraction amplitude persisted in the presence of atropine (1μM). Subsequent addition of PPADS (100μM) reduced neurogenic contractions in sham and irradiated tissues so that these were not significantly different from each other. In conclusion, irradiation reduced spontaneous and neurogenic contractions in the bladder in a region-specific and tissue layer-specific fashion. The presence or absence of the mucosal layer was found to be an important factor.