We evaluated an enzyme-linked immunosorbent assay (ELISA) for embryonic ζ-globin chains as a routine screening test for (--SEA) α-thalassemia deletion (SEA deletion). A total of 174 consecutive patient samples with a request for Hb analysis were recruited. The ELISA method was evaluated against a polymerase chain reaction (PCR)-based technique that was taken as the standard. Among 56 simple carriers of SEA deletion diagnosed by PCR and 112 subjects without the SEA deletion, the sensitivity and specificity of the ELISA method was 89.3–96.4 and 98.2–100%, respectively, depending on the cutoff value for optical density that was adopted. The ELISA method was able to detect both subjects with SEA deletion and concurrent β-thalassemia trait in this series, but only 1 out of 4 patients (25%) with Hb H disease. We speculate that incomplete lysis of hypochromic microcytic red cells together with the low red cell count in Hb H disease might account for the false-negative results. We showed that the ELISA method for embryonic ζ-chains was a sensitive method of screening for SEA deletion carriers at our locality, and should be easily adopted in a routine diagnostic laboratory. The method was rapid and also amendable to automation. In areas with a high prevalence of α-thalassemia, improved detection of SEA deletion carriers would ultimately facilitate the identification of pregnancies at risk of hydrops fetalis and its prevention through prenatal diagnosis.