The objective of this investigation was to compare the effect of vitamin A on limb development and limb regeneration in the same animal, at the same time, thus eliminating the possibility that species differences or different rates of uptake between animals would influence the results. Axolotl larvae had both right limbs amputated and then were treated with retinol palmitate by immersion at 60 or 300 mg l-1 for 4 or 10 days. Intact left developing limbs at the cone, two-digit, or four-digit stages responded to the treatment by deletion of skeletal elements producing hypomorphic limbs. Severity of the deletions was correlated with higher dose, longer times, and earlier stages of limb development. In contralateral right regenerating limbs, the effect of the same treatment was to cause various degrees of proximodistal duplication as well as occasional hypomorphic regenerates. Thus, there is a marked difference in response to vitamin A between developing and regenerating limbs. The implications of this observation are discussed especially with respect to the underlying morphogenetic mechanisms.