Immigrants looking to settle in the United States were not the only ones to cross the ocean on a ship and appear on a manifest. Depending upon the time period, passengers could also be: merchants and other businessmen soldiers returning to the United States native citizens returning from a trip abroad immigrants returning to the US from a return trip to their homeland I even found a manifest entry for a cousin who was a Red Cross nurse in Europe during World War I. If a passenger list entry is recent enough (generally late 19th century or later), it may give significant details about the passenger.
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