The antinociceptive action of the 2 main metabolites of thyrotropin-releasing hormone (TRH), pyroglutamyl-histidyl-proline (TRH-OH) and histidyl-proline-diketopiperazine or cyclo(His-Pro), were studied using mechanical (Haffner's test) and chemical (phenyl-p-benzoquinone writhing test) stimuli. TRH has previously been shown to be active against both these stimuli. TRH-OH showed an antinociceptive action against both stimuli, while cyclo(His-Pro) had a dose-dependent effect only against a mechanical stimulus. Both metabolites of TRH were less effective than TRH. The antinociception induced by TRH does not appear to depend on the biotransformation of TRH to its metabolites since they are less active than TRH itself.