BACKGROUND: In multiple sclerosis (MS), demyelination and neuroaxonal damage are seen in the hippocampus, and MRI has revealed hippocampal atrophy. OBJECTIVES: To investigate and compare hippocampal volume loss in patients with relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) using manual volumetry, and explore its association with memory dysfunction. METHODS: Hippocampi were manually delineated on volumetric MRI of 34 patients with RRMS, 23 patients with PPMS and 18 controls. Patients underwent neuropsychological tests of verbal and visuospatial recall memory. Linear regression was used to compare hippocampal volumes between subject groups, and to assess the association with memory function. RESULTS: Hippocampal volumes were smaller in MS patients compared with controls, and were similar in patients with RRMS and PPMS. The mean decrease in hippocampal volume in MS patients was 317 mm(3) (9.4%; 95% CI 86 to 549; p = 0.008) on the right and 284 mm(3) (8.9%; 95% CI 61 to 508; p = 0.013) on the left. A borderline association of hippocampal volume with memory performance was observed only in patients with PPMS. CONCLUSION: Hippocampal atrophy occurs in patients with RRMS and PPMS. Factors additional to hippocampal atrophy may impact on memory performance.