A variety of psychiatric disorders accompany multiple sclerosis (MS), affecting the spheres of cognition, affect, and personality. These disorders may be of primary and/or secondary nature, reflecting, respectively, neurologic damage and/or functional distress associated with a disabling disease. Evaluation of the nature, severity, and frequency of affective symptoms of MS patients is of importance to sensitize the treating physician to the possible need for specific psychiatric treatment. We conducted a prospective cross-sectional study assessing correlations of psychiatric symptomatology and the neurologic parameters of disease duration, disease activity (as expressed by the number of disease exacerbations per year), and disease severity (as measured by the Kurtzke Expanded Disability Status Scale [EDSS]) in 20 relapsing-remitting (RR)-MS patients. Patients were also evaluated by a semistructured psychiatric interview and the following rating scales: Hamilton Anxiety Scale (HAS), Hamilton Depression Scale (HDS), Hackett-Cassem Denial Scale, and Lubin Adjective Affective List. Results demonstrated a high prevalence of anxiety (90%) and to a lesser extent depression (50%) in RR-MS patients. Depression and anxiety were found to be associated with disease activity, but not with disease duration or severity. The mechanism of denial played a significant role in the psychiatric profile of the disease and was correlated with disease duration. We suggest that in RR-MS patients, psychiatric evaluation should also include assessment of defense and coping mechanisms, which in turn could guide specific individualized treatment.