Single nucleotides in higher plant organellar mRNAs are subject to post-transcriptional alterations by RNA editing, typically resulting in changes of the encoded protein sequence. Although some information has been acquired on the general features of the editing processes in both plastids and plant mitochondria, the mechanisms and factors involved in the selective recognition of the nucleotide to be edited are still unknown. To gain a better understanding of how an editing site is specifically selected by the organellar RNA editing machinery, we have attempted to rescue a previously generated tobacco plastid editing mutant. Using an interspecific protoplast fusion approach, we were able to restore RNA editing activity for a specific site in the psbF transcript that otherwise remained unedited. Our results suggest (i) that site-specific trans-acting factors mediate chloroplast editing site recognition and (ii) that these factors are of extraplastidic origin.