Besides its immunoregulatory effects, interleukin-4 (IL-4) has growth inhibitory activity on cells from human solid tumors, and IL-4 receptors are present on tumor cells including cells from head and neck squamous cell carcinomas. We have conducted a phase I/II trial in patients with oral squamous cell carcinomas of T(4), N(+) (1 exception) stage to assess safety and therapeutic activity of recombinant human (rh) IL-4 applying the drug intratumorally 3 times a week with dose escalation for a duration of 4 weeks. A total of 7 patients entered the study using doses of 1, 3, and 5 microg/kg. There was no reduction of tumor size with 1 patient showing clear progression of the tumor after 4 weeks of treatment. This, and the observation of limiting toxicity occurring as local pain at the injection site, led to study termination. Therefore, rhIL-4 cannot be recommended as an antitumor drug in this disease using monotherapy with the schedules applied in this trial.