Recently we have shown that thymus cells are required for, or facilitate, the differentiation of the B-cell population to be capable of producing a heterogeneous, high affinity antibody response to T-dependent antigens. This role of the thymus in B-cell differentiation will be investigated to determine: (a) the cell type involved; (b) whether the effect is mediated by a soluble factor; (c) whether the thymus has a similar role in regulating the differentiation of the B-cell population to produce a heterogeneous, high affinity antibody response to T-independent antigens; (d) whether thymus cells are involved in regulating the maturation of the B-cell population to be relatively resistant to tolerance induction; and (e) whether thymus cells are involved in regulating the maturation of the B-cell population to be capable of resynthesizing surface immunoglobulin following capping and shedding. Finally we will study the T-cell regulation of the changes in antibody affinity and heterogeneity which take place during the immune response.