Atrial natriuretic factor (ANF) lowers blood volume in intact and anephric experimental animals. The latter observation suggests extravasation of plasma at the level of the microcirculation. In view of the differential regional hemodynamic responses to ANF, the present study investigates possible regional differences in plasma extravasation measured as regional albumin clearances in skeletal muscle, lung, brain, ileum, and skin. In control animals, there were pronounced regional differences in clearances with highest values in ileum (0.248 +/- 0.015 microliter/min.g tissue) and lowest in brain (0.010 +/- 0.002 microliter/min.g tissue). Plasma-volume was 3.58 +/- 0.07 ml/100 g b.w. ANF (1 microgram/kg.min) significantly reduced plasma-volume (3.20 +/- 0.06 ml/100 g b.w.). This was associated with significantly increased albumin clearances in skeletal muscle and ileum, but not in other tissues examined. The data indicate that ANF increases albumin extravasation. This suggests that, besides effects on renal function and vascular tone, ANF also affects blood volume through influencing the relationship between intra- and extravascular volume.