Two subtypes of atrial natriuretic factor (ANF) receptors are present in vascular smooth muscle cells: B(biologically active) receptors coupled to a guanylate cyclase and C (clearance) receptors (95 per cent of the total number of ANF binding sites) non coupled to any identified second messenger system. We compared the homologous receptor regulation induced by ANF to the heterologous one elicited by angiotensin II (Ag II). Binding of (3-[125I]iodotyrosyl) rat ANF and cGMP production stimulated by ANF were measured after 18 hours preincubation of rat cultured vascular smooth muscle cells (10(6) cells/dish) at 37 degrees C with ANF or Ag II. The hormones (10 nM) decreased to the same extent the total apparent number of ANF binding sites (control: 208 +/- 25 fmol/10(6); ANF : 82 +/- 20 fmol/10(6) cells; Ag II : 90 +/- 9 fmol/10(6) cells) The diminution of the number of ANF binding sites induced by ANF exposure was reversed by 85 per cent following 10 minutes treatment of the cells with 10 mM AcOH. Moreover, treatment with ANF (10 nM) led to a diminution of cGMP stimulation induced by ANF, this effect being still present after washing the cells with 10 mM AcOH. In contrast, diminution of ANF building sites consecutive to Ag II exposure was not affected by AcOH treatment and a potentiation of cGMP production elicited by ANF was observed. These results suggest that, in rat vascular smooth muscle cells, B receptors are sensitive to homologous down regulation and C receptors are sensitive to heterologous regulation by Ag II.