SummaryOur experience on 107 cases of endogenous depression shows that L‐5‐hydroxy‐tryptophan is clinically effective. If we disregard the cases who showed improvement only after 4 weeks, more than half of the cases improved within a few weeks by L‐5‐HTP.We propose that endogenous depression is a disease in which biosynthesis of serotonin is periodically decreased, and this decrease is shown clinically as depression, and L‐5‐HTP, which penetrates into brain through blood brain barrier and is decar‐boxylated to form serotonin, may well be supplying serotonin the brain of depression needs.The dose used by us is rather low comparing to L‐DOPA dose on parkinsonism, and changes of serotonin or 5‐hydroxyindole acetic acid level in blood or cerebrospinal fluid may be very small, although still to be determined.As far as we have experienced, the administration of L‐5‐HTP for several weeks caused no severe side effects.The administration of L‐5‐HTP, we believe, opened a new approach to treat and analyse endogenous depression. Clinically, it is effective for the treatment and prevention of the depressive phase of endogenous depression. An important problem is why the biosynthesis of serotonin is decreased in endogenous depression, and this problem is to be solved to understand the ba