The Lazaretto quarantine station on the Delaware River was built beginning in 1799, in the aftermath of four devastating yellow fever epidemics, to protect Philadelphia from imported disease. Although historians of quarantine have focused on debates over the contagiousness of various diseases, far more important than the danger of contagion in the Lazaretto’s operations was “infection” in the ships themselves and in their cargo. This paper explores the elusive and misunderstood concept of “infection” in the nineteenth century through an examination of detention criteria and disinfection—or “purification”—procedures at the Lazaretto, as well as the rationale for the location of the quarantine station itself. I suggest that the critical elements of disinfection were not chemicals, but time and air—ideally, a particular kind of air in a particular kind of place. I also sketch the outlines of the “interpermeable world” prior to the Bacteriological Revolution, in which air, earth, water, and bodies were perceived as mutually permeable and always potentially health-promoting and pathogenic to varying degrees.