OBJECTIVE Parathyroid hormone-related protein (PTHrP), the main factor responsible for malignant hypercalcemia, is produced by a wide range of normal and malignant tissues. Prior studies in the rabbit model demonstrated that partial bladder outlet obstruction results in calcium-dysregulation characterized by a marked increase in free calcium within the smooth muscle compartment and the stimulation of calcium-activated enzymes, such as calpain and phospholipase A(2). METHODS Twenty-four male New Zealand white rabbits were divided into four groups of six each. Following 4 weeks of obstruction, one group of animals was killed, while outlet obstruction was reversed in two additional groups of animals, which were killed 4 and 8 weeks after relieving the obstruction. A group with six sham-operated rabbits served as controls. The expression and localization of PTHrP were detected in muscle and mucosa by immunohistochemistry, using a PTHrP-specific antibody. RESULTS In the sham-operated group, rabbit bladders showed a low expression of PTHrP in both the mucosa and muscle layers. PTHrP in the 4-week obstructed bladder group, in muscle and mucosa, were 266% and 134% higher than the sham group, respectively. Strong PTHrP immunostaining persisted in the 4-week reversal groups, but it returned to the sham level after 8 weeks of reversal in the muscle layer. As mentioned about the mucosa layer, the PTHrP level returned to control levels more rapidly after 4 weeks of reversal and continued after 8 weeks of reversal. CONCLUSIONS This study showed that PTHrP is increased after partial bladder outlet obstruction and decreased after relieving the obstruction.