The aim of this prospective study was to confirm whether and when a fall in gas transfer occurs following heart transplantation (HT); and to examine the potential relationship between gas transfer and haemodynamic change, immunosuppression, and cytomegalovirus (CMV) infection. The lung physiology of 34 heart transplant recipients (HTR) and 14 control patients undergoing coronary artery bypass grafting (CABG) were studied. The absolute and standardized residual values of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), residual volume (RV), forced residual volume (FRC), total lung capacity (TLC), transfer factor of the lungs for carbon monoxide (TL,CO) and carbon monoxide transfer coefficient (KCO) were measured before and at 30, 60, 90, 120 and 150 days after HT. These data were compared to haemodynamic status, graft rejection, cyclosporin levels and episodes of CMV infection. Lung function was studied in a group of patients before and 4 weeks after CABG. There was a significant fall in mean KCO after HT (pre-HT=1.29 and post-HT= 1.06 mmol · min-1 · kPa · L-1) but not after CABG (pre-CABG=1.49, post-CABG=1.5 mmol · min-1 · kPa · L-1. No relationship was observed between gas transfer and CMV. At the latest stage following HT (150 days) there was a positive correlation between TL,CO (absolute value and standardized residual) and mean cyclosporin level (r=0.48 and r=0.44, respectively) and also between the absolute KCO and actual (r=0.56) and mean (r=0.55) cyclosporin levels. Following HT, there is an early full in gas transfer, which is independent of the effects of surgery and bypass, implicating early immunosuppression (e.g. antithymocyte globulin/cyclosporin).