An overview of the epidemiologic studies of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) from 1945 through 1972 is presented. During this period 350 cases of ALS were documented. PD, which is apparently unique to the native Chamorro population, was not recognized during the early years of the study. A total of 213 PD patients have now been seen. The rates of both diseases have declined by approximately 50 per cent since 1965. In the early years incidence per 100,000 for ALS males approached 60; for females it was about 40. For PD males it was about 50; for females it was close to 20. The declines in both diseases have occurred in both sexes and at all age groups and no cohort phenomenon was observed. Marked geographic differences in the distribution of the diseases were observed with southern villages having the highest rates and western villages having the lowest rates; the remainder of the island was intermediate. Recent declines have been most marked in the southern high-rate villages. Chamorros living on the Island of Rota have rates similar to those on Guam; those on Saipan have lower rates. A possible excess of ALS among Filipino residents of Guam was noted; ALS has not been seen among other ethnic groups. Geographic mapping even in high incidence areas did not reveal true clusters or foci. Extensive case-control studies did not reveal any patterns of prior illness, life-style, or exposures distinguishing patients. A tendency for patients to be of somewhat lower socioeconomic level, have less education, eat more homegrown foods and raw meats, and have more contact with animals was found. No Mendelian genetic patterns were observed; males were affected more frequently than females for both diseases. Cases did not occur before age 20, reached maximum frequency between ages 55 and 65 and thereafter declined. Environmental factors associated with some aspect of the traditional way of life seem to be causally involved, but, since most aspects of the traditional life have changed in the past 50 years, the specific factors remain elusive.