This study was designed to test a path model depicting the relationships among social support, functional disability, perceived uncertainty, and psychosocial adaptation in 38 men and 80 women with multiple sclerosis, a chronic, unpredictable disease. Results from the regression analyses indicated that 35% of the variance in depression and 33% of the variance in purpose-in-life, respectively, were explained by age, sex, social status, and the perceived supportiveness and unsupportiveness of social network interactions. The path analyses showed that the perceived supportiveness of interactions was directly related to purpose-in-life but not to depression; both the direct path between the perceived unsupportiveness of interactions and adaptation and the indirect one through perceived uncertainty were related to depression and to purpose-in-life; and functional disability had a direct effect on adaptation, but the indirect path through perceived uncertainty was not corroborated.