Immune abnormalities have been reported in recipients of cellular and plasma blood products. To document the effect of current transfusion practices, we performed ex vivo lymphocyte immunophenotypic studies on patients with thalassaemia major who had received multiple (leucocyte-depleted) transfusions and patients with haemophilia A and B who had received heat viral-inactivated factor concentrates. Patients with thalassaemia major showed a significant lymphocytosis, with mainly B-cell changes consistent with ongoing B-cell stimulation associated with chronic exposure to red cell antigens. Reduced T-cell IL-2Ralpha expression would be consistent with inhibition by desferrioxamine chelation therapy. In contrast, patients with haemophilia showed predominantly T-cell changes. Patients with haemophilia A showed significantly elevated activated CD8+ cytotoxic T lymphocytes whereas those with haemophilia B showed an increase in CD8+CD11adim and CD4+CD45RA+ suppressor T cells. Several of the immune abnormalities found may be due to the presence of cytokines not removed by leucocyte filtration or destroyed by factor concentrate production (e.g. TGF-beta) causing a T-helper-2-like response. The extensive lymphocyte characterization in this study has not previously been performed and has enabled a closer examination of the functional lymphocyte immunophenotypes seen in patients treated according to current transfusion practices.