For the next eight years he remained in Philadelphia, during the winter months studying the collections made by him in summer excursions to various parts of the country east of the Mississippi, from the Great Lakes to Florida. Being absorbed in his studies and naturally reserved, Nuttall's social intercourse was limited. The families of the botanists and horticulturists of the time in Philadelphia—Prof. Barton, Zaccheus Collins, Reuben Haines, McMahon, from whom he named his genus Mahonia, William Bartram, and Colonel Carr—were almost his only acquaintances. To these he made visits, often of several days, from time to time. In Colonel Carr's house a room was expressly reserved for him. During this period he prepared also the description for his Genera of the North American Plants. Upon this work, which appeared in 1818, the reputation of Mr. Nuttall as a botanist principally rests. Prof. Torrey, in the preface to his Flora, declared that it had "contributed more than any other work to the advance of the accurate knowledge of the plants of this country." Nuttall turned his early trade to account by setting the type for the greater part of his book.
In 1817 Mr. Nuttall, already a Fellow of the Linnæan Society of London, was elected a member of the American Philosophical Society at the same meeting with Say and Schweinitz, and a corresponding member of the Academy of Natural Sciences of Philadelphia. He began to publish essays in the journal of the Academy, among the earliest being a description of Collinsia, a new genus of plants, named in honor of his friend and patron Z. Collins.
Nuttall had long desired to visit the Arkansas country, and soon after his American Plants was published Messrs. Correa de Serra, Z. Collins, William Maclure, and John Vaughan procured him the means of performing this long journey. Starting from Philadelphia on October 2, 1818, he reached the mouth of the Arkansas River about the middle of January and Fort Bellepoint on April 21:th. Thence he made expeditions in several directions, returning with abundant collections. He was on one of these trips in the middle of August, when, exhausted by long and difficult marches, made under the rays of a burning sun and in constant dread of the Indians, having suffered much from thirst, insufficient food, and exposure to the night dews, he was seized with a violent fever among the Osage tribe. The Indians robbed him of his effects and even threatened his life, but he finally reached the garrison at Bellepoint, where he remained sick until the middle of October. He made one more trip and then set out for home, reaching New Orleans February 18, 1820. He had then in sixteen months made a journey of more than five thousand miles, mainly over a country never visited before by scientific explorers, and still in the undisputed possession of the Indians.