Recombinant severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein was employed to establish an antigen-capturing enzyme-linked immunosorbent assay (ELISA). Antinucleocapsid protein antibodies could be detected in 68.4% of probable SARS patients 6 to 10 days after illness and in 89.6% of the patients 11 to 61 days after illness. No false-positive results were observed in 20 non-SARS fever patients, 24 non-SARS respiratory illness patients, and 20 health care workers. Among 940 other non-SARS clinical serum samples, only 1 was found to be weakly positive. This method provides a new, sensitive, and specific approach for SARS diagnosis.