The role of humoral autoimmune factors in the pathogenesis of motor neuron disease (MND) is currently under considerable scrutiny. In particular, there have been many reports of abnormal serum immunoglobulin patterns and elevated titres of anti-ganglioside antibodies in patients with MND. However, many of these studies may be biased by the selection criteria for patients and controls. In order to carefully address this issue we obtained 82 blood samples from consecutive MND patients identified through a national MND register in combination with 82 community controls matched for age, sex and geographical area. We used these samples to determine the frequency of monoclonal immunoglobulins (mIgs) and measure the levels of serum immunoglobulins and anti-GM1 ganglioside antibodies in sporadic cases of MND in comparison with normal controls. Serum mIgs detected using high resolution and immunofixation agarose electrophoresis were present in 1.2% of MND patients and 2.4% of controls. Using a highly sensitive isolectric focusing and immunoblotting method, monoclonal or oligoclonal immunoglobulins were found in 28% of MND patients and 27% of controls. Anti-GM1 antibodies were present in 26% of MND patients and 18% of controls (odds ratio = 1.5, 95%, CI 0.7-3.6) with no significant differences in titres between the 2 groups. Mean immunoglobulin G, A and M levels were equal in 2 groups. Thus, although alterations in these parameters were identified, we were unable to demonstrate any significant difference between MND patients and controls. We conclude that the majority of sporadic cases of MND are unlikely to have an autoimmune basis as judged by the lack of abnormalities in these parameters.