Motor neuron disease (MND) is a severely disabling, relentlessly progressive neurological condition with a marked reduction in life expectancy which might be expected to be associated with significant depression and psychological dysfunction following diagnosis. There is very little data on the incidence of depression in MND and most of the published evidence would suggest that depression is rare in patients with MND, especially when compared to other neurologically disabling illnesses. We have studied 40 patients with MND and compared them to a group of 92 patients with multiple sclerosis (MS) attending a neurology clinic. Depression was assessed using the Beck Depression Index (BDI) and the Hospital Anxiety and Depression Scale (HAD). There was no difference in incidence or severity of depression in these two patient groups. For the whole study group there was no difference in depression scores when compared by age, gender or marital status. Depression scores showed a weak association with increasing physical disability measured by the SF36 Physical Function scale for the MS group but there was no association between depression levels and SF36 physical function for the MND group. The MND group did, however, show a significant association between depression scores and pain measured by the SF36 scale. Anxiety levels (HAD scale) were shown to be significantly higher in females and married (versus single, widowed or divorced) subjects for the group as a whole. We conclude that depression is at least as common in MND patients as other neurologically disabled patients with MS and may often be associated with significant pain. Physicians and others involved in the care of patients with MND should be aware that depression and pain may be significant problems irrespective of the level of physical disability.