Using a new spectrophotometric assay, we found that human serum digests predominately (rC)n of (rI)n X (rC)n, in agreement with results of Nordlund et al. (Proc. Soc. Exp. Biol. Med., 1970, 133, 439-444) and DeClercq (Eur. J. Biochem., 1979, 93, 165-172) while rhesus monkey, cat, and rabbit sera digest primarily (rI)n. The results of Nordlund et al. also show (in agreement with our results) that human serum digests more of the (rC)n strand of (rI)n X (rC)n than rabbit serum. However, their results differ from ours, since they found that rabbit serum digests nearly equal, but small amounts of (rI)n and (rC)n. Results are discussed in relation to interferon (IFN) induction and toxicity following administration of (rI)n X (rC)n.