Anxiety and depression are widely distributed symptoms among multiple sclerosis patients and in the general population. We assessed the prevalence of anxiety and depression in the multiple sclerosis population in Nord-Trøndelag County, Norway compared with Norway's general population. The Hospital Anxiety and Depression Scale questionnaire was completed by 172 MS patients and 56,000 controls. A cut-off of > or =8 was used to define significant symptoms of anxiety and depression. Fatigue was measured using Krupp's Fatigue Severity Scale, with a mean cut-off of >4. Among men, 31.1% of the multiple sclerosis patients reported anxiety, while only 12.1% of the control population reported this symptom (p = 0.002). For women, the prevalence of anxiety was 29.7% versus 17.4% (p < 0.001). Depression was reported by 26.2% of the men with multiple sclerosis compared with 10.8% of the controls (p < 0.001). The corresponding figures for women were 25.2% versus 10.4% (p < 0.001). Anxiety and depression were not correlated with duration of disease or disability measured by the Expanded Disability Status Scale. Among women, fatigue was associated with anxiety (p < or = 0.010) and depression (p = 0.007). No such association was found among men. Anxiety and depression occur more frequently in multiple sclerosis patients than in the general population. Fatigue was associated with these neuropsychiatric manifestations in only women.