The phenotype and functional activity of circulating T and natural killer (NK) cells was investigated in a group of selected normal elderly donors in comparison with a group of normal young individuals. Old subjects exhibit a decline in circulating T cells and an impaired response to mitogens (Con A, PHA) associated with a relative increase in cells reacting with Leu 7 and Leu 11a monoclonal antibodies, directed against large granular lymphocytes with NK activity. The rise in circulating NK cells observed in the elderly was not associated with a concomitant increase in NK cytolytic activity against K 562 tumour cells, and time course kinetics of the cytotoxic reaction was similar to that observed in young subjects. When a greater than 95% pure population of Leu 11a+ cells from old individuals was sorted by flow cytometry and their functional cytotoxic activity examined, a significant decrease in NK cytotoxicity was detected. The target cell binding capacity of effector cells, morphologically evaluated at single cell level, did not differ in old and young subjects, even though bound cells from young donors have a higher lytic capacity. These data show that an increase in circulating NK granular lymphocytes occurs during human ageing, but suggest that in old subjects only a subset of NK cells is active in order to maintain a functional response similar to that observed in the young.