Blood pressure (BP), atrial and plasma concentrations of atrial natriuretic factor (ANF), hematocrit and renal glomerular ANF receptors were studied during the development of hypertension in two-kidney, one clip (2-K, 1C) rats and were compared with normotensive controls. Plasma ANF was elevated in the 2-K, 1C group in all stages of hypertension, even after 3 weeks when BP, although higher than in sham-operated animals, had not yet reached arbitrarily-set hypertensive levels. At this time, hematocrit was higher in the hypertensive rats than in the controls, but the difference later disappeared. Lower atrial ANF concentrations were observed in the 2-K, 1C group at week 3, but only in the right atrium. No difference in ANF levels was noted in either the left or right atrium between hypertensive and normotensive animals 5 and 7 weeks after clipping. The glomerular ANF receptor population was markedly smaller in the clipped left kidney of 2-K, 1C rats during all stages of hypertension, and in the untouched right kidney at 5 and 7 weeks after surgery, but was larger in the non-clipped right kidney in the pre-hypertensive phase (3 weeks). It is concluded that receptor density changes during the evolution of high BP in the 2-K, 1C Goldblatt model of experimental hypertension. Our data suggest that the increases and decreases in density of renal glomerular ANF receptors may play a role in the differential handling of sodium by the clipped and non-clipped kidney during the various stages of development of 2-K, 1C hypertension in the rat.