Pathogenic autoimmune cells are demonstrated to be able to produce neurotrophic factors during acute phase of multiple sclerosis (MS). In this study, we determined the production of various neurotrophins [brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin 3 (NT3) and neurotrophin 4 (NT4)] and some pro-inflammatory cytokines [tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)] by unstimulated peripheral blood mononuclear cells (PBMC) in 21 relapsing-remitting MS patients during different phases of disease (stable, relapse and post-relapse). During acute phase of disease, we detected a considerable increase of BDNF, TNF-alpha and IFN-gamma production, while significantly higher levels of GDNF, NGF, NT3 and NT4 were found in post-relapse phase. When neurotrophin production was correlated with clinical outcome (complete or partial recovery from new symptoms), we found a significantly higher BDNF production in relapse phase followed by increased GDNF, NGF, NT3 and NT4 levels during post-relapse phase in subjects with complete remission only. During relapse phase, we detected a significant increase of pro-inflammatory cytokines, that was more evident in patients with partial recovery. The neuroprotective potential of immune cells seems to be inversely correlated with disease duration and with the age of patients.