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Human factor D was purified, labelled with 125I and injected intracardially or intraperitoneally into male Sprague-Dawley rats. After intracardial administration, 80% of the radioactivity seen initially in the blood was eliminated within 5 min. The highest levels of radioactivity were recovered in the kidney cortex in both cases: maximally 24% of the total dose applied was recovered in this tissue 7 min after intracardial injection and 8-9% of the total dose 80-90 min after intraperitoneal administration. Significant amounts of radioactivity were also observed in the spleen, lungs, liver and heart muscle, but uptake by other tissues was very low. These results indicated that injected human factor D disappeared rapidly from the plasma of rats and uptake by the kidney cortex was one of the main routes of elimination.