1. The authors investigated the signal transduction in T-lymphocytes as a peripheral model for central neurons. 2. Intracellular free calcium concentration [Ca2+]i was measured using fura 2 in T-lymphocytes from 6 patients with major depression during and after depression and from 6 healthy controls. Patients were treated with interpersonal therapy (IPT) but not with psychotropic medication. 3. Phytohemagglutinin (PHA) triggers an oscillatory [Ca2+]i signal in human T-lymphocytes. This implies two mechanisms for [Ca2+]i regulation: inositol phophate (IP) mediated release from intracellular stores and [Ca2+]i influx from the extracellular medium. 4. PHA stimulates 49% of T cells from controls but only 17% of T cells from depressed patients. This finding explains previous results from cells in suspension indicating that [Ca2+]i signals after PHA-stimulation are reduced in cells from depressed patients. 5. Cells from depressed patients show less [Ca2+]i oscillations. Normal oscillation patterns are restored after clinical recovery from depression. 6. Thus altered [Ca2+]i oscillations in T-lymphocytes are a state phenomenon and may give us clues where to search for altered cellular mechanisms during depression.