We report here an evaluation of a program for thalassemia-disease prevention, comprising education, population screening for heterozygotes, and reproductive counseling; the evaluation includes cost analysis. A preprogram survey in 1978 of 3,247 citizens in the high-risk communities (85% were high-school students) showed that 88% favored a program but that only 31% considered fetal diagnosis as an acceptable option. Screening in high school or before marriage was preferred by 56%. In a 25-month period (December 1979-December 1982), we screened 6,748 persons, including 5,117 senior high-school students, using MCV/HbA2 indices. The participation rate was 80% in the high-school group. The frequency for beta-thalassemia heterozygosity was 4.7% with 10-fold variation among ethnic groups at risk; the overall frequency for all variants found was 5.4%. We surveyed 60 carriers and 120 noncarriers after screening high-school students (response rate 77%): most carriers told parents (95%) and friends (67%) the test result; and 38% of the carriers' parents (vs. 18% of the noncarriers' parents) were also screened. Carriers would ascertain their spouses' genotype (91%) and approved uniformly (95%) the high-school screening experience and its goal. We performed 11 fetal diagnoses in a 25-month interval (greater than 75% participation in target population) either by fetoscopy and globin-chain analysis or by amniocentesis and genomic DNA analysis; two of three affected fetuses were aborted at parental request, there was one spontaneous abortion (after fetoscopy), and seven live births. The at-risk couples claimed pregnancy would not be contemplated without the fetal-diagnosis option. We analyzed economic costs of the program: cost per case prevented is approximately equal to $ 6,700, slightly less than cost-per-patient-treatment-year or about 4% of undiscounted treatment cost incurred in the first 25 years of life for an affected individual. These findings indicate: collective acceptance of the program, appropriate attitudes among carriers, general acceptance and efficacy of fetal diagnosis, and global cost-effectiveness.