These findings indicate that i) adaptive immunity does not play a major role in protection from lethal SARS-CoV infection in mice, ii) the genetic absence of MyD88 significantly enhances SARS-CoV-induced morbidity and mortality , and iii) MyD88-dependent signaling through a receptor(s) other than IL-1R1 or IL-18R1 is responsible for protection from rMA15. Here, IL18R1 is linked to severe acute respiratory syndrome.