In an open, randomised study, 18 patients with clinically definite, relapsing-remitting multiple sclerosis (MS) received 1 microgram, 30 micrograms, or 1000 micrograms doses of recombinant gamma interferon (IFN-gamma), given by intravenous infusion twice a week for four weeks. 7 patients had exacerbations during treatment. This exacerbation rate, compared retrospectively with the pretreatment rate and prospectively with the post-treatment rate, was significantly greater than expected. Exacerbations were not precipitated by fever or other dose-dependent side-effects. A concomitant increase in circulating monocytes bearing class II (HLA-DR) surface antigen suggested that the attacks induced during treatment were immunologically mediated. IFN-gamma is unsuitable for treatment of MS.