A premarital screening program aiming at reducing the incidence of thalassemia major was started under the auspices of the Regional Health Administration in 1995 in the city of Denizli in the Aegean region of Turkey. In this report we assessed the 4-year results of the screening program. All couples who applied for marriage procedures were screened for β-thalassemia trait by automatic red cell indices and Hb A2 determination. The couples at risk were counseled and offered prenatal diagnosis and termination of pregnancy in case of an affected fetus. From October 1995 to August 1999, a total of 19,804 subjects (9,902 couples) were recruited for this study. The prevalence of β-thalassemia trait with increased Hb A2 was found to be 2.6% (514/19,804). In addition to the thalassemia trait, 22 patients (0.11%) had sickle trait. In 15 of the 9,902 couples, both partners were found to be carriers of the β-thalassemia trait. After genetic counseling, 2 of the 15 planned carrier marriages were canceled. Seven couples declared that they do not want to have a child at present. Prenatal diagnosis was sought by 6 couples. One fetus was found to be normal, 4 had thalassemia minor and 1 had thalassemia major; this pregnancy was terminated by elective abortion. This study indicated that premarital screening is a very useful tool for detecting carrier couples and an effective way of controlling thalassemia major.