We studied the role of the dopamine D2 receptor in physiological regulation of pain-related behavior. The experiments were performed in dopamine D2 receptor knockout mice and in their wild-type controls. Baseline sensitivity to thermal nociception was determined by measuring the response latency in the hot plate at three different stimulus temperatures and by determining the radiant-heat-induced paw withdrawal. Mechanical sensitivity was assessed by determining paw withdrawal responses to stimulation with a calibrated series of monofilaments. Intracolonic capsaicin was used to produce sustained pain-related behavior and referred hypersensitivity to mechanical stimulation. The hot plate response latencies were not significantly different between the dopamine D2 receptor knockout and wild-type animals, although the stimulus temperature-dependent decrease in the response latency was steeper in the wild-type group. The radiant-heat-induced paw withdrawal latency was slightly longer in the knockout animals. The number of capsaicin-induced behavioral responses or the latency to the occurrence of the first capsaicin-induced response was not different between the experimental groups. Dopamine D2 receptor knockout animals were more sensitive to mechanical stimulation of the hindpaws than wild-type animals both in the baseline condition and following development of capsaicin-induced referred hypersensitivity in the hindpaws. The results indicate that dopamine D2 receptors influence baseline nociception in the mouse, although this effect is weak and submodality selective. Additionally, dopamine D2 receptors may contribute to attenuation of referred hypersensitivity caused by sustained nociception.