An anterior pituitary was grafted into the breast muscles of male rats on day 5, or under the kidney capsule on day 30 or 60 of life. At the 70th day of life (rats operated at the 5th or 30th day) or at the 100th day of life (rats operated at the 60th day), rats were injected subcuta-neously with Freund''s complete adjuvant, being killed 2 days later. Rats pituitary-grafted at the 30th day showed a greater hyperprolactinemia than rats grafted at the 5th or 60th day. Submaxillary lymph node natural killer (NK) activity decreased in neonatally pituitary-grafted rats and increased in rats grafted at the 30th or 60th day of life, while lymph node cellularity decreased in rats grafted at the 30th or 60th day. In the case of lipopolysaccharide (LPS)- and concanavalin A (Con A)-induced cell proliferation in lymph nodes, the only significant factor detected was age of transplantation, the effect being less evident in older animals. To examine whether the autonomic denervation of submaxillary lymph nodes affected immune responses in pituitary-grafted rats, animals were subjected to a unilateral superior cervical ganglionectomy (Gx) and/or a parasympathetic decentralization (Dc; by chorda tym-pani section), 10 days before immunization with Freund''s adjuvant. A unilateral Gx blunted the stimulation of lymph node NK activity in rats receiving a pituitary transplant at the 30th or 60th day, but not at the 5th day. Only in sympathetically denervated lymph nodes a significant effect of pituitary transplants on LPS mitogenic effect was found, with significantly less effect of LPS in rats pituitary-grafted at the 5th or 30th day of life. Regarding Con A, a unilateral Gx or unilateral Gx plus Dc uncovered a significant depressive effect of pituitary transplants with a significantly smaller Con A mitogenic effect at each studied age in ipsilaterally Gx lymph nodes, and at 30 and 60 days of age in ipsilateraly Gx plus Dc lymph nodes. Pituitary grafts augmented Con A- induced proliferation in submaxillary lymph nodes at the 5th day of life while they decreased it at the 60th day of life. Pituitary transplants augmented cellularity at the sympathetically denervated lymph nodes and decreased it at the contralateral sham-operated side. Pituitary transplants also diminished lymph node cellularity at the Dc side, the effect being significant in rats transplanted at the 30th day of life. The results are compatible with age-dependent, inhibitory as well as promoting activities of hyperprolactinemia on immune responses in submaxillary lymph nodes, depending in part on intact autonomic nerves.