Thrombocytopenia is a frequent haematologic complication of IL-2 immunotherapy of cancer. Preliminary results suggest a role of melatonin in the regulation of platelet production, so a study was started to evaluate the influence of the pineal hormone on IL-2-induced thrombocytopenia. Of 25 lung cancer patients, 10 were treated with melatonin alone, 7 received IL-2 alone and 8 patients were concomitantly treated with IL-2 and melatonin. Thrombocytopenia occurred in 3/7 patients treated with IL-2 alone, and in none of those treated with IL-2 plus melatonin; this difference was statistically significant. Platelet number increased during IL-2 plus melatonin, even though not significantly; on the contrary, platelet number decreased during IL-2 alone. Platelet number observed in patients treated with IL-2 plus melatonin was significantly higher than in those who received IL-2 alone. Finally, melatonin alone did not substantially influence platelet number. These results show that melatonin may abolish IL-2-induced thrombocytopenia. This might be due to an inhibitory effect of melatonin on macrophage-mediated platelet destruction, with a following increase in platelet number due to an enhanced IL-3 production in response to IL-2.