From May 1985 to October 1987, 1,564 Southeast Asians living in Hawaii were screened for hereditary anemias. Microcytosis was determined by electronic red cell indices and morphology; iron deficiency was ruled out by normal red cell distribution width and normal protoporphyrin levels; Hb E was determined by electrophoresis; beta-thalassemia (thal) heterozygotes were identified by raised Hb A2 on column chromatography. alpha-Thalassemia heterozygotes were diagnosed by exclusion. Family studies helped identify or confirm diagnoses, especially for the alpha-thal-2 heterozygotes (-alpha/alpha alpha) and homozygotes (-alpha/-alpha). Provisional diagnoses are being checked by DNA analyses. Iron deficiency prevented detection of possibly coexisting alpha-thalassemias in 97 individuals. Technical problems included the obscuring of standard criteria for recognizing the alpha-thal variants by the presence of Hb E or beta-thal. In such cases, alpha-thal could only be detected by family studies or DNA analyses. Problems with hemoglobin (Hb) electrophoresis included Hb H migrating beyond the edge of the strip if incubation was not closely monitored, and difficulty in detecting the small amounts of unstable Hb Constant Spring. DNA analyses also had limitations, since the nondeletion alpha-thalassemias would not be detected by routine Southern blotting. DNA analyses suggested that about 50% of presumed alpha-thalassemias were alpha-thal-2 (-alpha/alpha alpha) variants, and a corresponding number of alpha-thal-2 variants were among the apparent normals. Gene frequencies in the unselected Lao subjects were approximately 0.2 for Hb E, at least 0.1 for (-alpha), usually a rightward (alpha -3.7) type, 0.04 for (-), and 0.01 for a beta-thal. Multistep screening for the alpha- and beta-thalassemias was an effective and efficient strategy.