Studies in mammals reveal that ablation of the sympathetic nervous system (SNS) can alter in vivo and in vitro parameters of immunity. To shed some light on the phylogenetic history of the interactions between the SNS and the immune system, we studied the effects of chemical sympathectomy on the proliferative response of frog splenocytes to mitogens. Adult Xenopus laevis were injected with 6-hydroxydopamine 3 days before removal of spleen cells for culture with mitogens. Splenocytes from sympathectomized frogs exhibited an increased proliferative response to the T cell mitogens PHA and ConA and the B cell mitogen, LPS. That sympathectomy appears to effect a release from tonic inhibition by the SNS in Xenopus is consistent with comparable experiments in mice. It also reveals a phylogenetically ancient origin for SNS-immune system communications.