Twenty pigs underwent (a) cystic duct occlusion by means of fluoroscopically guided transcatheter endoluminal bipolar radio-frequency (RF) electrocoagulation and (b) gallbladder sclerotherapy with one of two different regimens of ethanol and sodium tetradecylsulfate (STS). Serum ethanol levels and hepatic enzyme tests showed no acute toxicity. Postmortem histologic studies showed that the bile ducts beyond the occlusion site remained entirely unaffected in all animals. In three of four animals followed up for 2 weeks, the sclerosants induced necrosis of the gallbladder mucosa, but the adjacent liver, serosa, and blood vessels remained intact. In 13 of 16 animals followed up for 8 weeks, the gallbladder lumen was obliterated by fibrous scar tissue. In the animals treated with 95% ethanol and 3% STS, the gallbladder mucosa was necrotic in all areas after 2 weeks (two of two animals) and eradicated completely after 8 weeks (six of eight animals); the other regimen (70% ethanol plus 1% STS) was somewhat less effective. In this study, the combination of RF-mediated cystic duct occlusion and gallbladder sclerotherapy with ethanol and STS permitted gallbladder ablation in swine without toxic side effects.