INTRODUCTION: Interstitial cystitis (IC), sometimes referred to as IC/bladder pain syndrome, is a substantial health care problem. Once considered a rare, orphan disease, it is now believed to be relatively common. This pilot study was undertaken to determine if the combination of heparin and alkalinized lidocaine (heparin-lidocaine) was more efficacious than alkalinized lidocaine at relieving pain and urgency symptoms associated with IC and also capable of yielding higher lidocaine absorption. MATERIALS AND METHODS: A single blind study was conducted on 14 IC patients with a heparin-lidocaine combination versus alkalinized lidocaine instilled intravesically. In a separate study serum lidocaine levels for heparin-alkalinized lidocaine combination versus USP lidocaine only were determined by high performance liquid chromatography. RESULTS: Alkalinized lidocaine and heparin have been reported to provide relief from pain and urgency symptoms associated with IC. The heparin-lidocaine combination significantly reduced the % of bladder pain (38% versus 13%, p = 0.029) and urgency (42% versus 8% p = 0.003) compared to lidocaine. In addition the GAR was significantly better for the heparin-lidocaine combination at both 1 hr % improved (77% versus 50%, p = 0.04) and 24 hrs (57% versus 23%, p = 0.002) after study drug treatment. Serum lidocaine levels for the heparin-lidocaine combination were significantly higher compared to USP lidocaine (unalkalinized). The mean +/- SEM was 0.45 +/- 0.09 ?g/mL and 0.20 +/- 0.05 ?g/mL, respectively (p = 0.019). CONCLUSIONS: In this pilot study the heparin-lidocaine combination results in significantly better relief of IC symptoms compared to alkalinized lidocaine and the combination yields higher lidocaine absorption than USP lidocaine.