Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) has been shown to be transported from the brain to blood by a saturable system shared with Met-enkephalin and a few other substances. It is not known whether a similar system exists in the opposite direction. Accordingly, the entry rate of 125I-Tyr-MIF-1 from blood to brain was measured by a method involving perfusion of the test substances into the common carotid artery. The rate of entry was obtained from the slope of the line determined by brain to blood ratios at multiple points of time. Penetration of 125I-Tyr-MIF-1 across the blood-brain barrier was found to be 4.444 x 10(-3) ml/g/min, an entry rate significantly higher than that of the vascular marker 125I-albumin. Competition with Tyr-MIF-1 or nonradioactively labeled 127I-Tyr-MIF-1 showed no difference in rate of entry, indicating that the penetration of 125I-tyr-MIF-1 was not saturable. Met-enkephalin and Leu-enkephalin also failed to affect entry of 125I-Tyr-MIF-1. The results indicate that Tyr-MIF-1 can enter the brain from the blood to a greater extent than does albumin, but that this penetration does not involve a saturable system.