Urinary bladder inflammation has been observed in various disorders such as overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS). It is apparent that acetylcholine release is involved, yet other mediators and regulator chemicals may also contribute to modulating bladder function and sensation (1-3). An increased presence of inflammatory cells within the bladder and urine of patients suffering from OAB and IC/BPS may stimulate some dysfunction via the release of inflammatory mediators, known to modulate contractile activity in both the urothelium with lamina propria and the detrusor muscle (4, 5). Therefore, the involvement of immune cells and the various inflammatory mediators released at sites of inflammation is an important avenue to explore. This research aims to determine the effect of histamine on tonic contractions and phasic activity of the urinary bladder. Functional tissue baths containing adjacent strips of porcine urothelium with lamina propria (U&LP) or detrusor smooth muscle were mounted in gassed Krebs-bicarbonate solution at 37°C. Responses to histamine or various prostaglandin agonists in the absence and presence of selective receptor antagonists were examined. Data analysis of the responses was performed using a paired Student’s t-tests with p<0.05 considered significant. In the absence of any stimulation, strips of U&LP naturally develops spontaneous phasic contractions of 3.34 ± 0.06 cycles per minute (n=223) with an amplitude of 0.53 ± 0.02 grams (n=223). Both the histamine and prostaglandin receptor systems were capable of stimulating tonic and phasic contractions of urinary bladder urothelium with lamina propria and detrusor. The H1 histamine receptor subtype was determined to mediate U&LP increases in tonic contractions and also increase the frequencies of phasic contractions in response to histamine. In the presence of H1 receptor antagonists, increases in tonic contractions were significantly inhibited in both U&LP and the detrusor smooth muscle (pPGF2α>TXA2>PGD2>PGI2. Further investigation in the PGE2 receptor subtypes revealed that increases in contractions were not mediated via any of the EP receptors. This response appears to be mediated via the FP receptor in both U&LP and detrusor, suggesting some conversion of PGE2 to PGF2α upon contact with tissue. The preliminary findings of this research suggest that degranulation of mast cells infiltrating the bladder wall might induce increases to both tonic and phasic contractions of the urinary bladder via the actions on histamine and prostaglandin receptors. Future directions for this project aim to investigate the presence, prevalence and distribution of mast cells within the urinary bladder wall in various models of urinary disease and dysfunction. The influence of other infiltrating immune cells, such as lymphocytes, will also be explored generally in the lower urinary tract.