Because levels of plasma atrial natriuretic factor (ANF) increase with advancing age, a diminished hemodynamic responsiveness to ANF in the elderly has been hypothesized in the literature. Therefore hemodynamic effects after two infusion rates (0.25 and 2.0 micrograms/min) of atrial natriuretic factor (99-126) were investigated in young (n = 8) and elderly (n = 9) volunteers in a double-blind, randomized, and placebo-controlled protocol. After low-rate infusion, ANF concentrations increased to the upper normal range, and only minor effects were observed. In contrast, high-rate infusion resulted in a decrease in blood pressure and forearm vascular resistance, whereas an increase in heart rate was observed in both groups. Between young and elderly subjects, a significant difference was observed in the ANF-induced decrease in systolic blood pressure (mean +/- SD, -4% +/- 4% versus -12% +/- 7%, p less than 0.05) and mean arterial pressure (-6% +/- 5% versus -11% +/- 4%, p less than 0.05) during the high rate infusion. When compared with the concentrations of the young subjects, the ANF concentrations reached at both ANF dosages were higher in the elderly subjects; this was the result of a diminished ANF clearance in the elderly subjects. After correction of the changes of systolic blood pressure and mean arterial pressure for the higher ANF levels reached within this elderly group, no difference between young and elderly subjects remained. We conclude that a diminished cardiovascular responsiveness to ANF with advancing age could not be demonstrated. In contrast, the high-rate infusion of ANF induced an increased hemodynamic response in the elderly subjects, but this seems to be the result of the higher ANF levels reached within this group.