OBJECTIVE Previous studies have demonstrated that partial outlet obstruction and acute overdistension of the rabbit bladder rapidly stimulate the activation of similar patterns of gene expression. Since bladder overdistension has been shown to reduce the blood flow of the bladder and since unilateral ischemia of rabbit bladder has been found to induce similar physiologic and histologic changes to the bladder as found in association with partial outlet obstruction, we tested whether experimental ischemia of the rabbit bladder could induce the same molecular response. METHODS Unilateral ischemia was created by surgically ligating the major arteries entering the rabbit bladder to one side. Bladders were recovered from control rabbits and from rabbits at 1 hour, 8 hours, 1, 3, or 7 days after unilateral ischemia and were divided into ischemic and nonischemic portions. These tissues were used for in vitro 35S-methionine and 3H-thymidine incorporation assays. Ribonucleic acids extracted from these tissues were examined by Northern blot assay for the expression of a number of different mRNA transcripts. RESULTS 1) Bladder DNA synthesis was elevated 4-fold at 24 hours after ischemia; 2) protein synthesis was increased 2-fold at 8 and 24 hours after ischemia; 3) early response genes (c-fos and c-jun) mRNAs were induced by 1 hour of ischemia; hsp-70 mRNA was highly induced by 8 hours of ischemia, and bFGF mRNA was elevated 3- to 5-fold by 8 hours of ischemia. CONCLUSIONS The early molecular response of rabbit bladder to ischemia is similar to responses observed in bladder overdistension or partial outlet obstruction.