The following correlates of depression were examined in a sample of 166 patients with clinically definite relapsing-remitting (n=140) or secondary progressive (n=26) multiple sclerosis: (a) the present state of the patients' illness (i.e., whether or not they were currently experiencing an exacerbation of their symptoms); (b) their level of uncertainty concerning their illness; and (c) their strategies for coping with their illness. A current exacerbation in symptoms, greater uncertainty of illness, and greater use of emotion-centered forms of coping were all related to depression. Multivariate analyses revealed that uncertainty of illness played a pivotal role as a mediating variable. Exacerbations in illness appeared to heighten patients' levels of uncertainty, and it was largely through this heightened uncertainty that the increases in depression came about.