Plasma ANF concentration in uraemic patients is very sensitive to changes in extracellular volume. It is unknown, however, if the release of this vasoactive hormone has a compensatory role in the haemodynamic response to extracellular volume expansion in these patients. We investigated the effect of isolated ultrafiltration followed by isovolumic re-expansion by saline in seven haemodialysis patients. The experiment was repeated on two occasions and the UF rate as well as the rate of volume re-expansion in the two studies were accurately matched. During the phase of volume re-expansion, we infused either ANF (0.83 microgram/min) or a placebo, in random order and cross-over. Central venous pressure, arterial pressure, haematocrit, and plasma ANF concentration were measured in baseline conditions, after ultrafiltration, and 0, 15, and 30 min after isovolumic re-expansion. In the control experiment (placebo), isolated ultrafiltration caused a marked reduction in central venous pressure and in arterial pressure and a pronounced haematocrit increase. These changes were reversed by volume re-expansion. In the active experiment, during the phase of volume re-expansion ANF infusion doubled plasma ANF concentration as compared to control experiment but it did not affect the ongoing haemodynamic response nor the haematocrit changes. Doubling of plasma ANF concentration has no influence on the haemodynamic and microcirculatory adaptations to acute volume expansion in haemodialysis patients. The data indicate that it is unlikely that raised plasma ANF concentration has a major role in the cardiovascular response to acute extracellular volume expansion in these patients.