PURPOSE: Depressive symptomatology is frequently associated with interleukin (IL)-2 and interferon alfa-2b (INFα-2b) therapy in cancer patients. The objective of the present study was to evaluate the depressive and anxiety symptoms induced by IL-2 and/or INFα-2b in cancer patients during the first days of cytokine immunotherapy. PATIENTS AND METHODS: The study included 48 patients with renal cell carcinoma or melanoma. Patients were treated either with subcutaneous IL-2, alone (n = 20) or in combination with INFα-2b (n = 6); or with INFα-2b alone, administered subcutaneously at a low dose (n = 8) or intravenously at a high dose (n = 14). Depressive symptoms were evaluated using the Montgomery and Asberg Depression Rating Scale (MADRS), and anxiety symptoms were evaluated using the Covi scale. Evaluations were performed just before initiation of treatment (day 1) and on days 3 and 5 of treatment. RESULTS: Patients treated with IL-2 alone or in association with INFα-2b had significantly higher MADRS scores after 5 days of cytokine therapy, and patients who received both cytokines had increased scores on day 3. In contrast, patients treated with INFα-2b alone did not have varying MADRS scores during the course of treatment. Cytokine therapy had no effect on anxiety, except in patients treated with IL-2 in combination with INFα-2b. In these patients, the enhancement in anxiety scores that was observed on day 5 was mainly attributable to increased somatic complaints. CONCLUSION: IL-2 and INFα-2b have differential effects on mood, and IL-2 therapy induces depressive symptoms early in treatment.