The behavioural phenotype of mice lacking neuropeptide Y (NPY) Y(2)-type receptors was assessed in two well documented animal models of anxiety: namely, the elevated plus maze and the open field. NPY Y(2)-/- mice made more entries into, and spent significantly more time on, the open arms of the elevated plus maze when compared to their wild-type Y(2)+/+ controls (P<0.001). This effect was not due to non-specific changes in locomotor activity as the number of closed arm entries did not differ between groups. In addition, NPY Y(2)-/- mice displayed increased preference for the central area of the open field when compared to Y(2)+/+ animals (P<0.01), whereas total entries did not differ between groups. This study suggests that NPY Y(2) receptors may play an inhibitory role and supports the hypothesis that Y(2) receptors are involved in the regulation of anxiety-like behaviours by NPY.