The mutant axolotl Short toes develops with abnormal kidneys, Mullerian ducts, and limbs and provides one of the few experimental systems for developmental studies in amphibia. The present paper describes another deviation from this animal's normal physiology, which is very characteristic of the wild type: amputated limbs of Short toes fail to regenerate. A blastema is formed but differentiation does not occur. Detailed histological analysis provides evidence of abnormal formation of the basement membrane and accumulation of extracellular matrix within the blastema, which could be attributed to an imbalance of extracellular matrix and basement membrane proteins. The basement membrane develops much thicker and is convoluted in the arrested blastema of mutant animals. In contrast to the limbs, the tails of Short toes regenerated normally with no apparent abnormalities. No gross genomic aberrations have been detected between normal and mutant DNA, indicating that a large deletion or insertion is not likely to be the cause of this mutation.