N-terminal parts of proatrial natriuretic polypeptide have been proposed to be sensitive and specific markers of congestive heart failure (CHF). A prerequisite for use of a clinical marker is knowledge of day-to-day variation and dependence on age and sex. Immunoreactive N-terminal proatrial natriuretic polypeptide (31-67) (ir-N-ANP(31-67)) was measured in a clinically relevant population of healthy individuals. A total of 21 females (mean age 52 years, range 42-76) and 26 males (mean age 54 years, range 42-73), without cardiovascular disease, were included in the study. No correlation was found between ir-N-ANP(31-67) and sex. A statistically significant positive linear correlation ir-N-ANP pmol l(-1) = 182 + (8.2 x age in years) (p = 0.004) was found between age and ir-N-ANP(31-67). For the youngest subjects (42 years) the expected mean ir-N-ANP(31-67) was 530 pmol l(-1), and for the oldest subjects (76 years) it was 800 pmol l(-1). For all the subjects, the median ir-N-ANP(31-67) was found to be 626 pmol l(-1) (range 300-1151). The day-to-day variation was studied and no significant difference was found in the plasma concentration of two samples taken 2-5 days apart. Of the individual day-to-day variation, 95% would be expected to be in the interval from -244 to 188 pmol l(-1) (mean +/- 2 x SD). We conclude that ir-N-ANP(31-67) rises with age. The age-dependent rise in ir-N-ANP(31-67) is modest, but should be taken into consideration in order to use ir-N-ANP(31-67) as a diagnostic marker of CHF. The day-to-day variation is found to be rather high and cannot be neglected if N-ANP(31-67) is to be used as a marker of asymptomatic heart failure.