We studied 10 patients with melancholia before and after sleep deprivation and 8 controls with Tc-99m-hexamethylpropylenamineoxime (HMPAO) single photon emission computed tomography (SPECT). All depressed subjects showed relative hypoperfusion in the left anterolateral prefrontal cortex under both conditions. Only responders showed relative hyperperfusion in parts of the limbic system and a reduction of blood flow in these regions after sleep deprivation.