We evaluated the phagolysosomal fusion of peripheral blood monocytes from 15 patients with thalassemia major and 10 thalassemia major carriers using a cytomorphological method with acridine orange as fusion marker. The mono-cyte phagolysosomal fusion of thalassemic patients was decreased (49.6 ± 8.6%, mean ± SD) and differed significantly (p < 0.05) from those of carriers and normal controls (65.7 ± 11.4% and 74.6 ± 5.7%, respectively). In vitro deferoxamine partially improved monocyte phagolysosomal fusion of patients with thalassemia major, and did not affect monocyte function in carriers and healthy subjects. Furthermore, in vitro addition of ferrous sulfate decreased normal phagolysosomal fusion. We conclude that the monocyte phagolysosomal fusion dysfunction of thalassemic patients could be related to iron overload.