Research in the area of family issues and multiple sclerosis has mainly focused on the impact of multiple sclerosis on the spouse. The aim of the current study was to examine the relationship between patients' ratings of their spouses' responses to multiple sclerosis patient disability behaviors and the impact on patient psychological and physical functioning. Multiple sclerosis patients were interviewed over the telephone using standardized questionnaires to assess patient physical and psychological functioning, spouse responses to patient disability and well behaviors (i.e., how does the spouse respond when you're having difficulties related to multiple sclerosis?), and family environment factors. The study was set in a large university-based Multiple Sclerosis Clinical Center. Forty-four of 64 patients approached with definite multiple sclerosis participated in the study. Physical functioning was assessed by the Kurtzke-EDSS, SIP, SF-36, and psychological functioning was assessed by the CES-D and SF-36. Scores on the SF-36 were generally lower compared with a normative sample of individuals with major medical problems; however, mean Kurtzke scores of 5.60 reflected moderate to severe impairment. Exploring spouse responses to disability, correlation analyses revealed that solicitous spouse responses to patient disability behaviors were significantly associated with greater multiple sclerosis-related physical disability. This relationship was stronger for patients who were more depressed. Spouse negative responses to patient disability behaviors were associated with poorer mental health, whereas spouses' encouragement of patient well behaviors was associated with lower emotional distress. Poorer psychological functioning was found in patients with families who were reported to have higher conflict and/or who were more controlling. Higher levels of independence in families were associated with better psychological and physical functioning in the patients. These preliminary findings suggest that patients' perceptions of their families' responses to disability and family environment factors may be important areas for further research. The findings may also provide potential targets for clinical intervention in the future.