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The eugenics movement coincided with one of the greatest eras in U.S. immigration. During the first two decades of the 20th century, 600,000-1,250,000 immigrants per year entered the country through Ellis Island (except during World War I). Unlike earlier waves of immigrants who came primarily from northern Europe, the 20th century brought an influx from southern and eastern Europe. Eugenicists, most of whom were of northern and western European heritage, worried that the new immigrants weakened America biologically, and lobbied for federal legislation to selectively restrict immigration from "undesirable" countries.

The eugenics movement provided a scientific rationale for growing anti-immigration sentiments in American society. The earlier wave of Irish immigrants joined "established" Americans of northern and western European extraction in their disregard of "new" immigrants from southern and eastern Europe. Labor organizations fed on fears that working class Americans would be displaced from their jobs by an oversupply of cheap immigrant labor, and anti-communist factions stirred up fears of the "red tide" entering the U.S. from Russia and eastern Europe.

Eugenics Record Office Superintendent Harry Laughlin became the anti-immigration movement's most persuasive lobbyist. Between 1920 and 1924 he testified three times before the House of Representatives Committee on Immigration and Naturalization. He first testified that a disproportionate number of inmates in mental institutions were from southern and eastern Europe — even though his own data clearly showed a high proportion were German and Irish. On the strength of this testimony, Committee Chairman Albert Johnson appointed Laughlin as an "expert eugenics agent." In subsequent testimonies, Laughlin used flawed data to show that new immigrants had high levels of "all types of social inadequacy," including feeblemindedness, insanity, criminality, and dependency.

The Immigration Restriction Act of 1924, sponsored by Johnson, did everything eugenicists had hoped for. First, it limited total immigration to 165,000 — about 15-20% of peak years. More important, it restricted immigration from southern and eastern Europe countries to only 9% of the total. Northern and western European countries got 86% of the quota, even though they made up the minority of immigrants in 1923. This change in the complexion of immigration was accomplished by a cunning use of statistics. The Johnson Act limited immigrants from each country according to their proportion in the U.S. population in 1890 — a time prior to the major waves of southern and eastern European immigration when the U.S. was decidedly more Anglo-Nordic in composition.

U.S. immigration did not reach pre-Johnson Act levels again until the late 1980s. Less than 10% of the 660,477 legal immigrants to the U.S. in 1998 were from northern and western European countries.

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