Ts65Dn mice have an extra chromosome that contains a segment of chromosome 16 homologous to the Down syndrome 'critical region' of human chromosome 21. Since pain transmission and expression may be limited in people with mental disabilities, including Down syndrome, responsiveness to nociception in Ts65Dn mice was compared with that in their control litter-mates. In the formalin test, a model of tonic pain, Ts65Dn mice showed depressed sensitivity to nociception during the early and late phases. In the tail-flick test, they showed longer latencies than controls, but no differences among groups were observed in morphine responses. In the hot-plate test, no changes were observed in escape latencies during the first exposure, but Ts65Dn mice showed smaller tendency to lick. The results indicate that trisomic mice present an overall depressed responsiveness to nociceptive stimulation.