The small bowel (SB), an organ replete with lymphocytes, may provoke graft-versus-host disease (GVHD) after transplantation (Tx). Since tumor necrosis factor (TNF) has been suspected of mediating the tissue lesions of GVHD, we sought to determine whether TNF could be detected in the serum of rats undergoing GVHD after SBTx or lymphocyte transfer. For this purpose, postoperative serum TNF activity was determined in Lewis x Brown Norway (LBNF1) hybrid rats suffering from GVHD after undergoing transplantation of an entire (group 1; n = 8) or a segmental (group 2; n = 4) Lew SB, or after i.p. injection with lethal doses (500 x 10(6)) of Lew lymphocytes (group 3; n = 3). Control LBNF1 received i.p. small doses (50 x 10(6)) of Lew lymphocytes (group 4; n = 4). Serum TNF activity was assessed using the WEHI bioassay. In rats with acute and lethal GVHD after entire SBTx (group 1) or injection with large doses of lymphocytes (group 3), TNF activity gradually increased and reached high levels by the time the rats were agonal. In segmental SBTx rats (group 2), GVHD was less severe than in entire SBTx rats. Similarly, the increase in TNF activity was less intense and only transient since it had returned to control levels by the time the rats had completely recovered from GVHD. In control rats primed with small doses of lymphocytes (group 4), GVHD did not occur and no increase in TNF activity was detected.(ABSTRACT TRUNCATED AT 250 WORDS)