Although considered a mild disorder, beta thalassemia trait (uncomplicated by any other hematologic abnormality) has been reportedly associated with symptoms of anemia, while in other series hepatosplenomegaly has been reported as associated with this diagnosis. No controlled study has examined the symptoms and signs of individuals with beta thalassemia trait and compared these with age- and sex-matched normal individuals. We administered a questionnaire to 397 parents (67% females) of children with beta thalassemia major attending the National Thalassemia Centre in Kurunagala, Sri Lanka, and to 87 normal volunteers (90% females). All individuals underwent physical examination by the same investigator, as well as testing by automated cell counter (Coulter), and HPLC (Bio Rad). The mean age of the parents (33 years) and controls (29.5 years) was not significantly different. In parents with thalassemia trait, 20% of males and 42% of females complained of reduced exercise tolerance compared to 12.5% of males and 38% of females in the controls (P= NS). The questionnaire revealed that 41% of parents, and 36% of controls, complained of recurrent headache; 18% of parents, and 15% of controls, complained of lethargy (P=NS). A history of malaria infection was reported in 30% of parents with thalassemia trait, and in 24% of controls. Mean quality-of-life score, recorded formally by a linear analog scale, from 0 (poorest) to 10 (greatest) was 7.1 in parents and 7.2 in controls. Splenomegaly was detected in 6% of parents with beta thalassemia trait (mean spleen size 1.5 cm below the costal margin), and 5% of normal controls (mean spleen size 1 cm below the costal margin). These findings suggest that, by contrast to many reports in the older literature, in uncomplicated beta thalassemia trait there appears to be no symptoms or signs greater than those observed in a normal control population and that fatigue, lethargy, exercise intolerance, or splenomegaly in a patient with beta thalassemia trait should not be attributed to the underlying hemoglobinopathy.