By intravenous (bolus) administration of human recombinant tumor necrosis factor (2.5 X 10(6) units) into rabbits and monkeys it has been possible to follow its decay in the plasma and to determine the pharmacokinetic parameters. After labelling TNF with 125I, simultaneous determination of protein-bound radioactivity and bioactivity was carried out with the result that radioactivity decays somewhat slower than bio-activity suggesting that the use of the former tracer alone may underestimate TNF catabolism. Simultaneous determination of 125I-TNF in rabbit plasma and lymph after intravenous and subcutaneous administration indicated a lymph to plasma TNF concentration ratio of about 0.1 and 1 or more for the two routes, respectively.