Direction of weight change in depression has recently been reported to be mediated by Body Mass Index (BMI). The present study examined the relation between direction of weight change in unipolar depression, BMI, and clinical variables such as severity of depression, melancholia, chronicity and recurrence in 89 patients with major depression. While the BMIs of individuals who gained weight when depressed were significantly higher than individuals with no weight change, the BMIs of individuals who lost weight were not significantly lower than those with no weight change. Direction of weight change was not predicted by severity of depression, melancholia, chronicity or recurrence. Concerns regarding conceptual and methodological difficulties in research on predictors of direction of weight change in depression are discussed.