Background: We conducted a prospective, population-based study of ALS in the Republic of Ireland for the 3-year period 1995 to 1997., Methods: To ensure complete case ascertainment, multiple sources of information were used, including consultant neurologists, neurophysiologists, primary care physicians, and the Irish Motor Neuron Disease Association. The El Escorial diagnostic criteria for ALS were applied to all cases enrolled on the register and each patient was regularly followed up during his or her illness., Results: Between January 1, 1995, and December 31, 1997, 231 patients were diagnosed with possible, probable, or definite ALS, including 133 men (57.6%) and 98 women (42.4%). The average annual incidence rate was 2.1 per 100,000 person-years (95% CI, 1.8 to 2.4), and 2.8 per 100,000 person-years for the population older than 15 years (95% CI, 2.4 to 3.1). The incidence rate was higher for men, being 2.5 per 100,000 person-years (95% CI, 2.0 to 2.9), than for women, at 1.8 per 100,000 person-years (95% CI, 1.5 to 2.2), and increased with age for both sexes. The median age at onset was 64.2 years for men and 67.8 years for women. On December 31, 1996, the crude prevalence was 4.7 per 100,000 of the total population (95% CI, 4.0 to 5.5), and 6.2 per 100,000 for the population older than 15 years (95% CI, 5.3 to 7.1). Adjusting to the 1996 Irish population as standard, the incidence of ALS in Ireland during the 3-year study period is the third highest reported to date., Conclusions: There was a trend toward a higher incidence of ALS in the northwestern region of Ireland, although the numbers of cases involved were small and further study is required.