Summary Reduction in the size of rCn by sonic radiation caused a decrease in viscosity when complexed with rIn of high molecular weight but did not bring about a decrease in protective activity of the rIn:rCn against PVM or VSV viruses. Greater reduction in size of rCn by treatment with RNase resulted in progressive loss of capacity to complex with rIn and to protect against viral infections. The capacity of rIn:rCn to induce resistance to VSV virus in vitro and to PVM virus in vivo was more dependent upon maintaining a high molecular weight of rIn than of rCn. Activity was markedly diminished when the average molecular weight of rIn was below 1.9 × 105 and of rCn below 2.3 × 104.