For unknown reasons the incidence of non-Hodgkin's Lymphomas (NHL) has increased during the last decades. Conditions with impaired immune functions have been associated with an increased risk of malignant lymphomas. Interactions between the central nervous, immune, and endocrine systems have been recently identified, and the potential physiological importance of these interactions is being explored. In this prospective cohort study the potential association between an increasing incidence of depressive disorders and the development of malignant lymphoma is being explored. The participants were part of the Swedish manpower on sick leave between 1988 and 2000 with depressive disease for more than two weeks were followed until a diagnosis of lymphoid malignancy, death, emigration, or end of follow-up period. The final cohort included 87,677 individuals with 373,135 years of follow-up. There were 80 cases of NHL, chronic lymphocytic leukemia (CLL), and Hodgkin lymphoma (HL) with 70 cases expected. The first year of follow-up showed a slightly increased risk of NHL, which most probably can be interpreted as initial symptoms of lymphoma. We conclude that the increase in the incidence of malignant lymphomas observed during the last decades seems not to be associated with a concurrent increase of depressive disorders.