A battery of immunological functions was studied over a 2-year period in conjunction with a placebo-controlled trial of natural human alpha interferon in patients with multiple sclerosis. IgG synthesis was increased both systemically and intrathecally by administration of interferon; however, there were only minor changes in cerebrospinal fluid oligoclonal bands. Levels of helper and suppressor T lymphocytes fluctuated independently of clinical exacerbations, although mean helper/suppressor ratios were higher in multiple sclerosis patients than in controls and increased further during interferon treatment. Cerebrospinal fluid myelin basic protein and antibodies to basic protein were not affected by exacerbations or by interferon administration. Circulating IgG antibodies induced by interferon treatment appeared to be directed at a non-interferon contaminant of the preparation. None of the assays was a consistent indicator of disease activity or of clinical response to interferon.