Introduction. Tau protein is a potential marker of neuronal damage. The aim of the study is to investigate its potential role as a marker of brain atrophy in multiple sclerosis (MS).Materials and methods. Cerebrospinal fluid (CSF) and blood samples were collected from 48 patients with multiple sclerosis. Total-tau (t-tau) and phospho181Thr-tau (p-tau) concentrations were assayed with commercially available INNOTEST® hTAU Ag and INNOTEST® phospho181Thr-tau(181P) and correlated with indices of brain atrophy in magnetic resonance imaging (MRI) and clinical characteristics of the study population.Results. T-tau concentration in CSF was significantly higher in relapsing-remitting (RR) compared to secondary progressive (SP) MS patients (P = 0.01). Brain parenchymal fraction (BPF) was significantly decreased in SP patients (P = 0.002). BPF in the whole study population correlated inversely with Expanded Disability Status Scale (EDSS) (r = –0.51, P = 0.0002) and Multiple Sclerosis Severity Score (MSSS) (r = –0.42, P = 0.002). T-tau in CSF in the whole patient group correlated inversely with EDSS (r = –0.58, P = 0.0006).Conclusions. The results of our study suggest that total-tau concentration in CSF in a MS population decreases in the course of disease and reflects degree of parenchymal brain loss.