In a prospective, controlled, stratified, experimental effectiveness study of screening and counseling, 25 000 consecutive adults were screened for thalassemia trait. Eight hundred forty-three adults had a mean corpuscular volume less than 77 fL; 192 (22% of those with microcytosis) had hemoglobin A2 greater than 3.5%, proving beta-thalassemia trait. Video-program, neutral-educational, and patient-centered counseling methods produced equal levels of learning, retention, psychologic impact, and effects on life adjustment immediately and at 2 and 10 months after counseling. Ninety-nine percent of the patients told other persons about the counseling, and 43% had 106 others screened. Factors related to having someone else screened included plans to have children (p < 0.002), being younger (p < 0.0025), better education (p < 0.05), and having high knowledge of thalassemia (p = 0.05). For maximum effectiveness, screening and counseling programs should focus on patients for whom a positive result has high significance.