Studies of the ontogeny of immunity in a limited number of representative amphibians have shown that while the immune systems of the larval forms are competent to defend against potential pathogens in the temporary ponds they inhabit, they are not equivalent to the mature immune systems that develop after metamorphosis. Metamorphosis is a critical time of transition when increased concentrations of metamorphic hormones, principally thyroid hormones (TH) and corticosteroid hormones (CH), orchestrate the loss or reorganization of many tissues and organ systems, including the immune system. Immune system reorganization may serve to eliminate unnecessary lymphocytes that could be destructive if they recognized newly emerging adult-specific antigens on the adult tissues. Increased corticosteroids during metamorphosis appear to induce apoptosis of susceptible lymphocytes. This cell death can be inhibited in vitro or in vivo by the corticosteroid receptor antagonist, RU486. A coordinate increase in both TH and CH at metamorphosis may be common to all amphibians that undergo metamorphosis. Current evidence suggests that the central hypothalamic mediator that induces pituitary production of both thyroid-stimulating hormone and adrenocorticotropic hormone in larval amphibians is corticotropin-releasing hormone. Most amphibians probably survive the temporary immunosuppression associated with metamorphosis with no deleterious effects. However, it is hypothesized that if environmental stressors result in the induction of metamorphosis at a less than optimal body size and state of immune maturation, the immune system destruction would be more significant, and the amphibians could be at greater risk of infection and death.