Recombinant interleukin-2 (rIL-2) is at present widely applied in the immunotherapy of various advanced cancers. As a number of side effects following the administration of rIL-2, either alone or in combination with lymphokine-activated killer (LAK-) cells, have been reported, a preparation of human leukocyte-derived and fully glycosylated interleukin-2 was used in the present study. We have recently demonstrated in cats that this natural IL-2 (nIL-2) is well tolerated and that the distribution and elimination half-lifes following intrathecal (i.th.) application are considerably longer than those after intravenous (i.v.) injection. To determine whether these long half-lifes and the good tolerance of i.th. given nIL-2 are also found in man, four patients with meningeosis neoplastica received repeated injections of human nIL-2 i.th.. Cerebrospinal fluid samples were drawn at different time intervals from either the lateral ventricle or lumbar subarachnoid space. The doses of nIL-2 ranged from 2 x 10(4) to 4 x 10(5) IU per injection. Only minor side effects were noted in one patient. The half-lifes for distribution and elimination of i.th. given nIL-2 ranged between 0.5-1.7 hours and 4.9-14.4 hours respectively. A linear relationship exists between the i.th. dose of nIL-2 and the area under the cerebrospinal fluid activity time profile curve.