1. This study was designed to investigate the antinociceptive activity of capsaicin in acute and persistent nocifensor behavioural models and to determine whether this was mediated via a specific receptor interaction, by use of the antagonist, capsazepine. 2. Capsaicin administered systemically in low doses produced antinociception in the knee joint hyperalgesia, rat paw pressure, rat and mouse tail flick and mouse hot plate nocifensor models with similar efficacy in all tests. 3. The novel competitive capsaicin antagonist, capsazepine, prevented the capsaicin-induced antinociception when administered systemically in the range 50-100 mumol kg-1. 4. Capsazepine administered by itself had no antinociceptive actions. 5. These data describe a joint hyperalgesic model in the rat which does not rely on extreme nocifensor behavioural endpoints and it is suggested this is a useful model for investigating mechanisms in persistent pain. 6. This is the first demonstration of antagonism by capsazepine of the behavioural antinociceptive properties of capsaicin and provides further evidence that capsaicin acts to reduce nociceptive thresholds via a specific receptor.