Little is known about CD4(+) T-cell immunity to the severe acute respiratory syndrome (SARS) coronavirus. In two SARS patients, we examined the memory CD4(+) T-cell responses to peptides derived from SARS coronavirus structural proteins. We generated CD4(+) T-cell lines to 3 peptides from the spike (S) protein and defined their HLA restriction. In one patient, the predominant memory CD4(+) T-cell response was directed against an epitope outside the S protein receptor-binding domain. In both patients, the frequency of CD4(+) memory T-cells to virus structural proteins and anti-SARS coronavirus IgG levels were low by 12 months after infection. This report expands our understanding of the specificity and duration of anti-SARS coronavirus CD4(+) T-cell immune responses.