The relationship between major depression and the salutogenic construct of sense of coherence was investigated. The Sense of Coherence scale and the Beck Depression Inventory were administered to 50 patients diagnosed with major depressive disorder and to 50 control subjects. Significant negative correlations were found between scores on Depression and total scores on the Sense of Coherence scale as well as all three of its subscales (Comprehensibility, Manageability, and Meaningfulness). A significant positive correlation was found between scores on the Sense of Coherence scale and age. Of the three subscales, a low score on Meaningfulness was the best predictor of scores on Depression.