We have conducted an ambidirectional study to estimate the incidence of equine motor neuron disease (EMND) in the northeastern US. The clinical and pathological features of EMND are similar to those described in human motor neuron disease. We have also collected data on all EMND cases reported in the US and described the geographic distribution of the disease. To identify factors associated with the risk of EMND, the authors assembled 163 control horses from the population in which cases were identified. The significance of association between the hypothesized factors and the risk of EMND was evaluated using the logistic regression analysis and the risk was estimated using the odds ratio. Seventy-eight horses in North America were diagnosed with EMND between the period of January 1985 and November 1993. Most of the cases were identified in the Northeast of the US and the incidence of EMND appears to be increasing in this area. Factors found to be significantly associated with EMND were breed and the age of the horse. Quarter horses were the only breed with a significantly higher risk of EMND (odds ratio = 2.3). The risk of EMND increased with age, reached a peak around 16 years of age and then declined. The sex of the horse was not associated with the risk of the disease.