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Rush reports that his sister is in grave danger and that, by popular demand, physicians have been forced to adopt his treatment for the fever.

Rush defends his taking in Johnny Stall and Ed Fisher, as neither had any other home. His sister, who was at the brink of death, is better, but his mother is now ill and is refusing treatment.

Rush writes that he has seen 100 patients, and that he now saves almost all those he sees within the first day. He notes that some doctors rail against the cure he uses, several of them publishing false information, even though they generally have not visited patients with the fever. He chronicles the fate of several doctors that have contracted the disease. He notes that some of his friends are ashamed to see him once they fall ill. He admonishes her once more to watch the boys closely for signs of infection, for the fever will lie dormant 1 to 16 days following contraction.

Rush notes that the fever has increased more in one week than it had in three weeks in 1793 and 1797. He had made plans to leave in 7-10 days when the U. S. Mint was closed, but by the end of the letter announces more immediate plans to remove to Sydenham, which has been prepared for the family and servants. Their son John is arriving via his ship in New Castle. A note was appended to the letter in 1848, saying that the close of the letter was cut out for an autograph seeker.

Rush reports that he was driven to Rosehill to visit their son, Ben, and also met neighbors. He figures that two-fifths of all those sent to Bush Hill hospital have died, because his remedies were not used.

Rush relates how he misses Julia, then describes the activities of their boys. He notes that the weather has been uncommonly cool, which has damaged crops. There has also been an outbreak of yellow fever in the city, but he expects it to be checked by the cool weather. He points out that the "ejection of Mr. Erskine's convention with our government by the British Court" has caused outrage in the city.

Rush updates Julia on the alarming spread of the fever. He reports that the College of Physicians has met to consult on how to stop the spread of disease and to draw up instructions for that purpose. These directions will be handed to the mayor. He asks her to stay in New Jersey with the children, and to pray for his protection, although he takes all precautions possible. He plans to confine his boys to the house for their protection.

Rush states that the boys are so apprehensive about contracting the fever from his clothes that he has decided to send them to Trenton. He asks her to have them read something useful, because he is worried about possible habits of idleness. He notes that the directions from the College of Physicians are to be published tomorrow, but worries that the fever will not subside before October's heavy rains and frost. His postscript provides instructions on how to protect the boys.

Rush notes that both boys have headaches, but are travelling regardless. He reports on the fever in their neighborhood, listing who has died or left town.

Rush notes that rain and cold weather have not decreased cases of the fever; 700 have died since 11 October, and 3400 since 1 August. He feels the distress of others all the more because he cannot assist them now. He has discovered further evidence that his sister gave her life to save his. Finally, he notes that his publications are still saving lives.