A case of inadvertent intra-arterial self-injection of crushed codeine tablets in an 87-year-old man, resulting in gangrene of an upper extremity, is presented. The problem studied was whether the gangrene was caused by the codeine or by one of the excipients found in the tablets. The cause of the gangrene was investigated in an experimental study. Each of the components of the tablet (codeine, lactose, gelatin, carboxymethyl cellulose, calcium stearate, talc, and microcrystalline cellulose) was injected into the femoral arteries of dogs. The results of the study clearly demonstrate that the unique component producing the gangrene was the microcrystalline cellulose, while the injection of pure codeine was harmless. To date, the only reported deleterious effects of intravascular injection of microcrystalline cellulose have been pulmonary embolism and granulomatosis. Some examples of drugs that include microcrystalline cellulose are methadone, methaqualone, oxcycodone, acetaminophen, aspirin with codeine, propoxyphene napsylate, meprobamate, and phenobarbital. Recently, the vulnerability of drug addicts who habitually inject drugs into veins to the accidental injection of an artery has been noted, and it seems likely that in the future the problem of intra-arterial injection will increase in severity. The literature of the last 40 years is reviewed, and a list of drugs known to have produced gangrene when injected intra-arterially is cited.