This study has investigated the patterns of membrane 2H4 (CD45RA) and UCHL1 (CD45RO) expression by CD4+ and CD8+ lymphocyte subpopulations in 10 adults and seven children with common variable immunodeficiency (CVI) and X-linked hypogammaglobulinaemia (XLA). Of the 10 adults (CVI, n = 8; XLA, n = 2), only one with a diagnosis of CVI showed normal CD45R expression. For the remaining seven adult CVI patients the abnormal CD45R profiles were primarily associated with CD4+ lymphocytes in three and CD8+ lymphocytes in four. Specific increases in CD45RA- CD45RO+ fractions were found in four CVI patients and in all of these there was a concomitant reduction in circulating CD19+ B-cell numbers. Two of the CVI cases were identical twin sisters and both had the same CD45R abnormality. The two adults with XLA also showed abnormal CD45R expression (increased CD45RA+ CD45RO- components) but of particular note, in view of the fact that these were brothers, one was associated with the CD4+ subpopulation and the other with the CD8+ fraction. Similar analyses for the paediatric group revealed, in distinct contrast to the adult patients, no significant abnormalities of CD45R expression suggesting that these defects may not become apparent until a later age. Further investigations of in vitro lymphocyte proliferation (PHA and PWM) in the eight adults with CVI showed a significant correlation between abnormal responses and disordered CD45R expression. It is proposed that these abnormal patterns of CD45R expression by lymphocyte subpopulations in CVI and XLA may be of fundamental importance with respect to the pathogenesis of these particular immunodeficiencies.