Molting and regeneration of lost appendages are tightly-coupled, hormonally-regulated processes in decapod crustaceans. Precocious molts are induced by eyestalk ablation, which reduces circulating molt-inhibiting hormone (MIH) and results in an immediate rise in hemolymph ecdysteroids. Precocious molts are also induced by autotomy of 5–8 walking legs; adult land crabs (Gecarcinus lateralis) molt 6–8 wk after multiple leg autotomy (MLA). Autotomy of one or more of the 1° limb buds (LBs) that form after MLA before a critical period interrupts proecdysis until 2° LBs re-regenerate and grow to the approximate size of those lost. Based on these observations, Skinner proposed that limb buds produce two factors that control proecdysial events. Limb Autotomy Factor–Anecdysis (LAF_an), produced by 1° LBs when at least five legs are autotomized, stimulates anecdysial animals to enter proecdysis. Limb Autotomy Factor–Proecdysis (LAF_pro), produced by 2° LBs in premolt animals when at least one 1° LB is autotomized, inhibits proecdysial processes. Initial characterizations suggest that LAF_pro is a MIH-like polypeptide that inhibits the synthesis and secretion of ecdysteroid by the Y-organs.