Recent work in our laboratory has demonstrated that prostaglandin (PG) D2 and the enzyme activities for its biosynthesis and inactivation are highly concentrated in the olfactory bulb and that the mitral cell layer of the bulb is enriched with PGD2-binding protein. We therefore investigated the role of PGD2 in the processing of odor signals in the rabbit olfactory bulb by an electrophysiological technique. Iontophoretic (-100 nA, 20 s), intra-arterial (0.0125-0.1 mg/kg) and intravenous (i.v., 0.05-0.3 mg/kg) administration of PGD2 enhanced and prolonged the responses of mitral cells to some of the olfactory stimuli tested. The extent and duration of granule cell inhibition of mitral cells were assessed by recording field potential responses in the bulb to paired lateral olfactory tract volleys. The i.v. administration of indomethacin or diclophenac, both of which are inhibitors of PG biosynthesis, resulted in prolongation of the granule cell inhibition of mitral cells without any significant change of the conditioning amplitudes. It also caused the reduction of the spike responses of mitral cells to olfactory stimuli. After treatment with indomethacin, the i.v. administration of PGD2 (1 mg/kg) rapidly reduced the duration of the granule cell inhibition of mitral cells. These results indicate that PGD2 plays a modulatory role in the mitral cell responses to odor stimuli by suppressing the inhibitory synaptic inputs from granule cells to mitral cells.