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1867–1873: Helios, photographer of the American West

Muybridge returned to San Francisco on 13 February 1867 a changed man. Friends and associates later stated that he had changed from a smart and pleasant businessman into an eccentric artist. He was much more careless about his appearance, was easily agitated, could suddenly take objection to people and soon after act like nothing had happened, and he would regularly misstate previously-arranged business deals. His care about whether he judged something to be beautiful had become much stronger than his care for money; he easily refused payment if a customer seemed to be slightly critical of his work. Photographer Silas Selleck, who had known Muybridge from New York since circa 1852 and had been a close friend since 1855, claimed that he could hardly recognize Muybridge after his return.

Muybridge converted a lightweight two-wheel, one-horse carriage into a portable darkroom to carry out his work, and with a logo on the back dubbed it "Helios' Flying Studio". He had acquired highly proficient technical skills and an artist's eye, and became very successful in photography, focusing principally on landscape and architectural subjects. An 1868 advertisement stated a wide scope of subjects: "Helios is prepared to accept commissions to photograph Private Residences, Ranches, Mills, Views, Animals, Ships, etc., anywhere in the city, or any portion of the Pacific Coast. Architects', Surveyors' and Engineers' Drawings copied mathamatically (sic) correct. Photographic copies of Paintings and Works of Art."

Muybridge constantly tinkered with his cameras and chemicals, trying to improve the sales appeal of his pictures. In 1869, he patented a "sky shade" to reduce the tendency of intense blue outdoors skies to bleach out the images of the blue-sensitive photographic emulsions of the time. An article published in 2017 and an expanded book document that Muybridge heavily edited and modified his photos, inserting clouds or the moon, even adding volcanos to his pictures for artistic effects.