Demuth began to experiment with tempera during this period, including several floral works. Tempera, and later oil, proved most suitable to the solidity of his subsequent architectural works. Demuth's architectural paintings took as their subject those factories, smokestacks and grain elevators that symbolized the explosive growth of American industrialization during the early part of the twentieth century, as uniquely manifest in his Lancaster home.

In August of 1921, Demuth departed on his fourth and final trip to Europe. By September, his ill heath prompted him to check into the American Hospital, at Neuilly-sur-Seine. He was treated for what would later be diagnosed as diabetes. He returned to the United States in November.

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