BACKGROUND AND PURPOSE: Attention is one of the major cognitive domains adversely affected in multiple sclerosis (MS). The aim of the current study was to determine the effect of a single dose of methylphenidate on cognitive performance of MS patients with significant attention deficit. METHODS: In a double-blind placebo-controlled study design, 26 MS patients with impaired attention were randomly assigned to receive a single dose of 10 mg methylphenidate or placebo. Attention was assessed using the paced auditory serial addition test for 3 and 2 s (PASAT3'' and PASAT2'') at baseline and 1 h after drug/placebo administration. RESULTS: Methylphenidate significantly improved performance of both PASAT3'' and PASAT2'' tests by 22.8% and 25.6% respectively (p<0.001), while no significant changes were observed in placebo treated patients. CONCLUSION: Administration of a single dose of methylphenidate significantly improved attention in MS patients with considerable attention deficit.