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A good jumping-off point is Arequipa. Acclimatize while taking in the sights, then head to the Colca Canyon. The four-hour drive travels over Patapampa Pass, for views of the Valley of the Volcanoes, and through the Reserva Nacional Salinas y Aguada Blanca, where herds of wild vicuñas, llamas, and alpacas graze. At the canyon you can go on a multiday hike or relax at a resort, but nearly everyone comes to spy condors at Cruz del Condor. Afterward, head back to Arequipa and on to Puno and Lake Titicaca, where you can book an overnight island homestay, visit the floating islands, or see the Sillustanti ruins. From Puno some head to Bolivia, while others go to Cusco by train, bus, or plane. Similarly, you can travel to Puno from Cusco and begin your exploration in the opposite direction.
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