Many animals can regenerate lost appendages, but for unknown reasons their regenerative capacity varies with species, appendage and developmental stage. Now, Takeo Kubo and colleagues reveal that the development of the immune system impacts negatively on the regeneration of Xenopus tadpole tails (see p. 2323). Tadpoles can regenerate amputated tails, but briefly lose this ability during the so-called refractory period (embryonic stage 45-47) for some reason. By comparing gene expression profiles at wound sites following tail amputation before, during and after the refractory period, the researchers discovered that immune responses differ between these three periods; during the regenerative periods, they are either not yet established or well matured. Intriguingly, suppressing immune responses during the refractory period, using pharmacological agents or by depleting immune cells by knocking down the transcription factor PU.1, restores regenerative capacity. These findings establish, for the first time, a direct link between an organism's regenerative capacity and its immune responses. Future studies should show whether this link is conserved in other systems.