General practitioners (GPs) are recommended to use DSM-IV criteria to diagnose major depression in daily clinical practice. This implies the assessment of nine depressive symptoms and four additional criteria. A short structured interview has been developed to assess these symptoms and criteria, and a study was carried out to investigate the reliability and validity with which GPs can assess these symptoms and criteria and the DSM-IV diagnosis of major depression. In 14 general practices, 52 patients with symptoms of distress and depression were interviewed twice by their GP, with an interval of one to four days. Furthermore, the patients filled out three depression questionnaires. The reproducibility of eight symptoms and three additional criteria was moderate to good (kappa >0.40). The reproducibility of the depressive symptom count, that is necessary to arrive at a diagnosis of major depression, was such that in 75 percent of the patients the test-retest difference did not exceed one symptom. The reproducibility of the diagnosis of major depression was good (kappa 0.63). The validity of the diagnosis of major depression assessed by the GPs, as compared to results of the self-report depression questionnaires, was satisfactory (r 0.35-0.61). Diagnosing major depression in patients with depressive symptomatology just above or below the threshold of major depression warrants a certain amount of caution in general practice.