Acquired urinary incontinence (AUI) in the bitch is a debilitating incurable condition hypothesised to be hormonally related as it affects 20% of neutered (Arnold et al., 1989) vs. <1% of intact bitches (Holt et al., 1993). AUI in the bitch is associated with a decreased maximal urethral closure pressure but this is not a defining attribute and its exact pathophysiology remains unknown. In post menopausal women UI is linked with changes in percentage collagen within the bladder and detrusor instability (Charlton et al., 1999). The aim of this study was to determine if neutering alters the collagen percentage in the canine urinary bladder wall. Sections (2cm x 2cm) of bladder (lateral dome) were dissected from entire and neutered male and female dogs (ME, MN, FE and FN) euthanased by barbiturate overdose with informed owner consent. Dogs were of varying breed, weight (7-45kg) and age (1-14yrs). Tissue was fixed in 10% phosphate buffered formalin, wax embedded and sectioned (2µm) for Masson Orange G stain. Images (5 sections/bladder) were evaluated morphometrically by light microscopic stereologic analysis (40X) to determine collagen percentage. Data are expressed as mean ± s.e.mean (n= No. of dogs), with statistical differences determined by ANOVA (Bonferroni post-test). Percentage collagen in the bladder was significantly increased (P<0.001) in FN 49.4±3.3 (n=8), compared to FE 19.4±2.2 (n=12), ME 19.5±1.3 (n=21), and MN 20.3±1.1 (n=9). There was no difference between percentage collagen in ME, MN or FE groups and there was no effect of weight or age on statistical analysis. The increase in collagen in the FN occurs due to greater collagen deposition between and within muscle bundles. This has the potential to affect bladder function by altering action potential conduction. Strikingly this result contrasts with our previous work (Coit et al., 2006) which showed that neutering causes a marked decrease in the bladder responsiveness to muscarinic and neurogenic field stimulation equally in both sexes. The loss of gonadal oestrogen, following neutering, has been put forward as a cause for AUI. As oestrogen prevents proliferation of fibroblasts and the deposition of collagen in coronary vessels (rats) (Blacher et al., 2000) we postulate that a lack of oestrogen, following neutering in the bitch, may contribute to the observed increase of collagen within the bladder wall. While this increase may predispose bitches to AUI, the sex difference in this study clearly suggests another mechanism underlies the change in bladder responsiveness. This will require further study but could lead to the development of new targets and therapies for treating AUI in both humans and dogs.