This is an open-label, randomized, multicenter, comparative, and parallel-group study comparing the therapeutic effects of two interferon-beta-1a regimens in relapsing-remitting multiple sclerosis (MS). The primary objective is to demonstrate the superiority of Rebif® 44 microgram (mcg) subcutaneous injection given three times a week (132 mcg per week) to that of Avonex® 30 mcg intramuscular injection given once a week.

Inclusion Criteria:

• Age between 18 and 55 years
• Clinically definite or laboratory-supported definite relapsing-remitting MS according to Poser's criteria
• Two or more relapses within the preceding 24 months
• Clinical stability or improving neurological state during the 4 weeks before Study Day 1
• Expanded disability status scale (EDSS) score from 0 to 5.5, inclusive
• Two or more lesions consistent with MS on a Screening proton density/T2-magnetic resonance imaging (MRI) scan to be performed 28 plus/minus (+/-) 4 days before the Study Day 1 MRI
• Willingness and ability to comply with the protocol for the duration of the study
• Written informed consent given before any study-related procedure not part of the subject's normal medical care, with the understanding that the subject can withdraw consent at any time without prejudice to future medical care
• For female subjects, lack of childbearing potential must be satisfied by either being post-menopausal or surgically sterilized or using a hormonal contraceptive, intra-uterine device, diaphragm with spermicide or condom with spermicide for the duration of the study. Subjects should neither be pregnant nor breast-feeding; confirmation that the subject is not pregnant will be established by a negative serum human chorionic gonadotropin (hCG) pregnancy test within 7 days of Study Day 1 (the pregnancy test will not be required of subjects who will be post-menopausal or surgically sterilized)

Exclusion Criteria:

• Secondary progressive MS, primary progressive MS or progressive relapsing MS
• Prior use of interferon
• Treatment with oral or systemic corticosteroids or adrenocorticotropic hormone (ACTH) within 4 weeks of Study Day 1 or within 7 days before the Screening MRI
• Psychiatric disorder that is unstable or will preclude safe participation in the study
• Significant leucopenia (white blood cell count less than 0.5 times the lower limit of normal) within 7 days of Study Day 1
• Elevated liver function tests (Alanine transaminase [ALT], Aspartate transaminase [AST], alkaline phosphatase or total bilirubin greater than 2 times the upper limit of normal) within 7 days of Study Day 1
• Prior cytokine or anti-cytokine therapy or glatiramer acetate within the 3 months before Study Day 1
• Immunomodulatory or immunosuppressive therapy within the 12 months before Study Day 1, including but not limited to cyclophosphamide, cyclosporin, methotrexate, azathioprine, linomide and mitoxantrone
• Previous use of cladribine or total lymphoid irradiation
• Allergy to human serum albumin, mannitol or gadolinium diethylenetriaminepentacetic acid (DTPA)
• Intravenous immunoglobulin or any other investigational drug or procedure in the 6 months before Study Day 1
• Systemic disease that can interfere with subject safety, compliance or evaluation of the condition under study, such as insulin-dependent diabetes, Lyme disease, clinically significant cardiac disease or infection with human immunodeficiency virus (HIV) or Human T-cell lymphotrophic virus, Type-1 (HTLV-1)