Interferon (IFN)-beta is generally considered an effective treatment for multiple sclerosis (MS); however; some patients do not respond to this therapy possibly due to the production of neutralising antibodies (NAB) which can prevent the biological effect of IFN-beta. We compared the two types of IFN-beta, the glycosylated IFN-beta (1a) and the non-glycosylated IFN-beta (1b) as their chemical differences may entail differing immunogenic capacities. We studied 22 relapsing-remitting MS patients treated with IFN-beta (1a) and 31 treated with IFN-beta (1b) for 1 year, using the same assay and criteria, to compare the two types of IFN-beta in their ability to induce binding and neutralising antibodies and examined the correlation of the findings with the clinical data. Binding antibodies to IFN-beta (1a) and IFN-beta (1b) were determined by enzyme-linked im munosorbent assay. A bioassay was used to detect and quantify the NABs to IFN-beta, measuring the capacity of NABs to block the antiviral resistance induced by IFNs. Binding antibodies were found in 32 % of those treated with IFN-beta (1a) and in 52 % of those treated with IFN-beta (1b); NABs were found in 14% and 24 %, respectively. Both groups showed a significant decrease in relapse rate during the first year of treatment. These results demonstrate that the IFN-beta (1b) molecule is more immunogenic than the IFN-beta (1a) molecule. This may be due to the non-glycosylated, chemical structure of the former, which can produce aggregates and enhance antibody production. No association was found between the presence of NABs and the clinical status of the patients.