A line of transgenic tobacco expressing the coat protein (CP) of potato virus X (PVX) was resistant against a broad spectrum of PVX strains. Inoculation of leaves and protoplasts with PVX expressing the jellyfish green fluorescent protein reporter gene revealed that this resistance mechanism suppressed PVX replication in the initially infected cell and systemic spread of the virus. Cell-to-cell movement was also slower in the resistant plants. The resistance at the level of replication was effective against wild-type PVX and also against movement-defective isolates with a frameshift mutation or deletion in the CP ORF. However, the cell-to-cell movement defect of the mutant viruses was rescued on the resistant plants. Based on these results it is proposed that the primary resistance mechanism is at the level of replication.