The effects of orchidectomy on the structure and function of lymphoid tissues in mice have been studied. Both pre- and postpuberal orchidectomy caused relative hypertrophy of the thymus. There was also an increase in size of peripheral lymph nodes to reach a sustained maximum (6 weeks). Sychronous thymectomy and orchidectomy prevented the lymph node enlargement that follows orchidectomy alone. Enlargement of the thymus was due to increased numbers of thymocytes, and it could be abrogated by administration of androgens. Orchidectomy was associated with an acceleration of rejection of skin allografts which was prevented by androgen administration and abrogated by antilymphocyte serum. The reactivity of orchidectomized mice to sheep red blood cells and the early response to oxazolone, which is limited by thymus-processed cells, was increased, whereas production of antibodies to oxazolone, skin allografts, and pneumococcal polysaccharide was unchanged. It is suggested that orchidectomy increases cell-mediated immune responses but has no direct effect upon responses that are mainly dependent on B cells. Orchidectomy prolongs the interval between the subcutaneous injection of methylcholanthrene and the appearance of subcutaneous sarcomas. In tumour transplantation experiments orchidectomy casued protection against the Meth A tumour grown in ascitic or subcutaneous form. This protection was counteracted by antilymphocyte serum and partially countered by adult thymectomy combined with orchidectomy. In contrast, the appearance in AKR mice of spontaneous leukaemia, a tumour known to be thymus dependent, was increased after orchidectomy. The results of experiments with hypopituitary mice suggested that the effects of orchidectomy on immune response result from androgen withdrawal rather than interference with the hormonal milieu.