In Xenopus, as in mammals, there is a functionally significant bidirectional communication between the neuroendocrine and immune systems. In this review, we describe the evidence for the neural innervation of Xenopus lymphoid organs, review the effects of neurotransmitter and hormone manipulations on measures of immunity, and discuss the role of hormones on immunological changes during metamorphosis. We also speculate as to the phylogenetic significance of these data, and outline possible areas of future research.