The nucleotide sequence of the aphid nontransmissible Campbell isolate of cauliflower mosaic virus has been determined between the BstEll and XhoI sites, the region known to be associated with aphid transmission. Comparison of the DNA sequence with that of the aphid transmissible isolates revealed no gross structural alterations in any of the open reading frames (ORFs). Recombinant DNA hybrid constructs and in vitro alteration of ORF VII were used to verify that ORF VII was not involved in the regulation of the downstream ORF II. Instead, a modification within a small region of ORF II which alters only one amino acid of the potential protein product relative to the aphid-transmissible isolate was found to be responsible for the lack of aphid transmission in the Campbell isolate.