The effects of atrial natriuretic factors (ANF) on cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) production by isolated renal tubules and glomeruli from rats has been investigated. ANF (1 micromolar) increased cGMP accumulation in isolated glomeruli 35-fold and in isolated inner medullary collecting ducts 20-fold. Small increases in cGMP accumulation were seen in response to 1 micromolar ANF in other nephron segments: proximal convoluted tubules, proximal straight tubules, thin descending limbs, medullary thick ascending limbs and cortical collecting ducts. Dose response studies revealed that the threshold for an increase in cGMP accumulation was 0.1-1 nanomolar ANF in inner medullary collecting ducts, and was 10-100 nanomolar in glomeruli. The threshold concentration for a response in inner medullary collecting ducts was approximately the same as reported circulating levels of ANF in control rats. ANF (1 micromolar) did not alter cAMP accumulation in the absence or presence of vasopressin in medullary thick ascending limbs or in inner medullary collecting ducts. Based on these results, we have initiated transport studies in isolated perfused inner medullary collecting ducts to determine whether ANF affects urea, water, or sodium chloride transport.