Symptoms associated with interstitial cystitis (IC) (urinary frequency, urgency and pain) resemble those in cats diagnosed with feline IC (FIC). Patients with IC also show enhanced sensitivity to intravesical application of KCl solution. In the current study we compared the effect of bladder distention and intravesical infusion of KCl solution on Adelta bladder afferent nerve activity in normal and FIC cats. Cats were anesthetized with alpha-chloralose (60 to 70 mg/kg intravenously). Single and multiunit afferent nerve activity was recorded with platinum electrodes from fibers dissected from the transected pelvic nerve. Bladder Adelta afferents were activated by bladder distention at constant pressures (5 to 80 cm H2O) by infusing saline or KCl solution (80 to 300 mM). Increasing bladder pressure by saline infusion over a range of constant pressures (5 to 80 cm H2O) increased afferent firing in normal and FIC cats. However, the slope of the pressure-firing curve was significantly steeper in cats with FIC. In normal cats KCl infusion (80 to 300 mM) into the bladder produced a pressure-firing curve similar to that induced by saline infusion. However, in FIC cats KCl at concentrations of 150 to 300 mM produced almost complete inhibition of afferent firing at pressures between 30 and 80 cm H2O. These data suggest that 1) bladder Adelta afferents in FIC cats are more sensitive to pressure changes than are afferents in normal cats and 2) the inhibition of afferent firing by high concentrations of KCl in FIC cats is likely the result of afferent nerve depolarization and it is consistent with the idea of increased permeability of bladder epithelium in FIC.