The present study tests the hypothesis of a negative association between patients with schizophrenia, manic-depressive psychosis and acute appendicitis. Using the nation-wide Danish case registers the occurrence of acute appendicitis among up to 20,402 inpatients with schizophrenia and up to 10,281 inpatients with manic-depressive psychosis and ten individually matched control persons for each psychiatric patient was investigated. A case-control and follow-up design was applied. Persons who developed schizophrenia had a significantly decreased relative risk of acute appendicitis of 0.49 before and of 0.59 after first psychiatric admission. Similarly the occurrence of manic-depressive psychosis was associated with a decreased relative risk of acute appendicitis of 0.50 before and of 0.70 after first psychiatric admission. One or more unknown factors inversely affect the risk for the subsequent development of psychoses and acute appendicitis. Further studies of this relationship may help to clarify etiological or pathophysiological aspects of schizophrenia and manic-depressive psychosis.