Laparoscopic surgery frequently requires tattooing of endoscopically identified sites for localization during surgery. Some tattooing agents cause serious tissue injury, which must be recognized in pathologic examination. Seven surgically resected colons were reviewed after injection with methylene blue or India ink at intervals of 1 day to 7 weeks before surgery. Early reactions to India ink included necrosis, edema, and neutrophilic infiltration in the submucosa and muscularis propria. Vessels were inflamed but without fibrinoid necrosis. Early reactions to methylene blue included ischemic ulceration, necrosis, and eosinophilic infiltration in the submucosa as well as fibrinoid necrosis of vessel walls. In the repair of methylene-blue injury, obliterative intimal fibrosis was seen in vessels. Such changes were absent in the colons injected with India ink. The India ink remained remained visible with the naked eye and microscopically 7 weeks after injection. Methylene blue was not grossly visible 7 days after injection, and only microscopic particles of pigment remained in widely scattered macrophages. In light of these findings, the amount of ink injected should be minimized and the injection site should be completely resected at surgery. Methylene blue is a poor tattoo agent, but its occasional use continues, and pathologists should recognize the resulting reaction.