To develop a mathematical model of the distribution and metabolism of rat corticotropin-releasing factor (rCRF), the time course of 125I-labelled rCRF in plasma was measured in male Sprague-Dawley rats (i) following a rapid injection of 24 ng rCRF/100 g body weight (BW), or (ii) following a rapid injection of 424 ng rCRF/100 g BW, or (iii) during an infusion at a rate ranging from 0.28 to 0.73 ng rCRF X min-1 X 100 g BW-1. The comparison of the one-, two-, and three-compartment models shows that the two-pool structure fits better to the dynamics of CRF in plasma as measured in each rat. Following a rapid injection the decay curve occurs in a biphasic manner; the early phase of disappearance is 25 times faster than the late one. There is no significant difference between the estimates of the metabolic clearance rate following both amplitudes of injection (0.40 +/- 0.06 and 0.48 +/- 0.05 mL X min-1 X 100 g BW-1). The volume of the first pool, 16.8 +/- 1.1 mL/100 g BW, is four times larger than the plasma volume. It would thus appear that CRF is rapidly distributed from plasma into several tissues which are represented in the first pool of the model. The mean residence time of every CRF molecule in the second compartment, from the moment of secretion to its elimination, is from three to four times longer than in the first one. It stays, on average, between 140 min and 3 h in the system before an irreversible exit.(ABSTRACT TRUNCATED AT 250 WORDS)