The ontogeny of the proliferative response of Xenopus thymocytes to the T-cell mitogens concanavalin A (Con A) and phytohaemagglutinin and to the B-cell mitogen E. coli lipopolysaccharide (LPS) is examined during the first 2 years of life. Responses after metamorphosis are compared with those occurring in the spleen. During much of larval life, mitogen-treated thymocytes display no sign of elevated [3H]TdR uptake. A low level in vitro response to Con A and LPS emerges transiently just prior to metamorphosis, the latter period being associated with a temporary disruption of thymocyte mitogen reactivity. Appreciable stimulation of both thymocytes and splenocytes with all three mitogens emerges within the first few months post-metamorphosis, and, with the exception of the thymocyte response to LPS, these induced proliferative levels are maintained or increased in toadlets aged 7-24 months. Maximal levels of LPS responsiveness in thymocyte cultures are found at 6 months of age. LPS-induced thymocyte proliferation at this time is confirmed morphologically by autoradiography; furthermore, immunofluorescence experiments, using an anti-Xenopus-mu chain antiserum, reveal that LPS induces the differentiation of cytoplasmic IgM cells in both spleen and thymus. The results indicate the presence of substantial populations of mitogen-sensitive cells in B lineage in the anuran thymus.