Correspondence Professor Ian R Mackay, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic. 3800, Australia. Email: ian.mackay@med.monash.edu.au Areas of the world in which hepatitis B virus (HBV) infection is endemic are diminishing progressively due to improved hygiene and nutrition, elimination of HBV from blood supplies, and vaccination. Yet, in some countries, there is still a pool of carriers of HBV, representing a continuing potential source of new infections. Acute HBV infection is often subclinical, such that the risk of chronicity among acutely infected healthy individuals is hard to estimate, although previously cited figures of about 10% can be realistically downgraded to about 5%. 1 However, this risk is increased substantially by any cause of immunological deficiency, whether this be a result of immaturity exemplified by neonatal infection, debilitating disease such as renal failure exemplified by past outbreaks of HBV infection in dialysis units, or malnutrition often accompanying intravenous drug use. Such global states of immunological deficiency in humans are revealed by antigenic challenge; for T cell deficiency by impaired expression of cutaneous delayed type hypersensitivity using a panel of microbial test antigens; 2 and for B cell deficiency by a decreased capacity for specific antibody synthesis after immunization. 3 These immune response deficits are acquired in contrast to the likely wide, although as yet unascertained, range of deficits that are genetically determined. Of these genetic deficits, two in particular were investigated by Cheong et al ., whose article appears in this issue. 4