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Two strains of cucumber mosaic virus (CMV) differed in three characteristics of value for cross-protection experiments. Their virions and also two of their double-stranded RNAs could be separated and distinguished by electrophoresis on polyacrylamide gels, and the symptoms of one strain were milder than the other in tobacco, tomato, and squash. The mild strain, CMV-S, protected plants of these three hosts from the effects of the second strain, CMV-P, and also prevented the accumulation of virions and ds RNAs of the challenge strain. Protection was detected in leaves inoculated with the challenge strain and also in later formed leaves. The only exception to this result was the accumulation of ds RNAs and to a lesser extent virions of the challenge strain when infectious viral RNA was used as the challenge inoculum instead of virus particles. This breakdown of cross protection occurred only in those leaves inoculated with the challenge strain RNA. No accumulation of challenge ds RNAs or virions occurred in later formed leaves. Tomato and tobacco plants infected with CMV-S were not protected from infection by tobacco mosaic virus.