Sex-related differences in the lower urinary tract (LUT) activity responding to intravesical infusion of diluted acetic acid (A/A, pH 3.0) were investigated during cystometrograms in decerebrate unanesthetized mice. A/A produced a decrease of inter-contraction intervals in both female and male animals, and the extent of the decrease in male mice was much less than that in female mice (19 ± 5 %, P=0.03 versus 65 ± 5 %, P=0.03, respectively; n=6 for each) exhibiting a marked difference between the two groups in response to acid irritation of the LUT (P=0.002). A/A reduced maximal voiding pressure (MVP) (19 ± 4 %, P=0.03) but had no effect on pressure threshold for inducing voiding contraction (PT) (P=0.56) in females, whereas A/A did not change MVP (P=1.00) but increased PT (16 ± 4 %, P=0.03) in males. A/A decreased bladder compliances of both female and male mice in a similar fashion (44 ± 10 % versus 24 ± 7 %, P=0.03 for each). In male mice, A/A produced persistent dribbling of fluid after voiding contraction phase, which was virtually not seen in females. The present study demonstrated the differences between female and male mice in response to noxious stimulation in the LUT: the female bladder is more sensitive to the acid irritation, while the male urethra is more irritable to the noxious stimulus. Identification of mechanisms underlying sex-specific characteristics might be helpful for elucidating pathogenesis of painful bladder syndrome.