The penetration of four radioiodinated materials-Tyr-MIF-1, DAMGO, tyrosine, and albumin-into the periventricular tissue after ICV injection was studied in rats by film autoradiography. Rates of disappearance from the CNS for the injected compounds were also determined by computer-assisted image analysis of the autoradiographic images. The four materials showed distinct patterns of dispersion from the ventricular system, with Tyr-MIF-1 moving farthest into the parenchyma of the brain and albumin primarily restricted to the ventricular space. The other two compounds, tyrosine and DAMGO, had intermediate values. Tyr-MIF-1 also displayed the fastest rate of removal from the brain, which may represent the ability of the peptide to gain access to sites of saturable transport. By contrast, the exit from the brain of DAMGO was minimal, whereas the efflux of albumin and tyrosine was intermediate. These results show the utility of these methods in the simultaneous measurement of both the patterns of distribution within the CNS and the rates of removal from the CNS of compounds injected into the brain.