Rats, receiving an intrathecal pretreatment of oligodeoxynucleotide complementary to c-fos mRNA (antisense), showed no increases in Fos protein or preprodynorphin messenger RNA in the outer laminae of the lumbar spinal cord when challenged 4 h later with a 50 microliters intraplantar injection of 5% formalin. Animals pretreated with saline or sense oligodeoxynucleotide showed marked increases in Fos protein (2 h after formalin challenge) and preprodynorphin mRNA (20 h after formalin challenge) in the lumbar region of the cord ipsilateral to the side of the injection. The behavioural consequences of antisense pretreatment were an increase in the formalin-induced licking/biting responses during the tonic, but not the acute phase. These observations could be interpreted as representing a sequence of events beginning with the formalin-induced increase in the transcription factor Fos, which in turn increases the synthesis of preprodynorphin messenger RNA resulting in the production of the dynorphin opioid peptides which then exert a modulatory antinociceptive action.