In a pilot study the safety and therapeutic effects of an immunostimulatory intralymphatic treatment with natural human interleukin-2 (IL-2) in combination with zidovudine were evaluated in nine patients with AIDS. Therapy with IL-2 consisted of one subcutaneous injection of 0.1 microgram/kg IL-2, followed by four intralymphatic IL-2 infusions of 0.1 microgram/kg each within a period of up to 15 days. Enlargement of lymph nodes was seen in six and a transient increase of CD4 cells in five out of nine persons in association with the IL-2 therapy. An increase of HIV p24-antigenemia was observed only in the two patients in whom zidovudine dosage had to be reduced because of side effects. Moderate clinical side effects occurred in eight of the nine patients. Four patients developed zidovudine associated anemia. Six participants showed a favourable course of disease with survival of 25 to 54 months (median 30 months) despite a previous diagnosis of manifest AIDS before IL-2 therapy. This pilot study demonstrates that a combination therapy with intralymphatic IL-2 and zidovudine can induce positive immunomodulatory effects, even in the presence of manifest AIDS. Further studies should explore the tolerability and effects of a prolonged therapy with IL-2 in combination with a more potent antiviral drug combination therapy.