Thermo-sensory mechanisms are little understood. The protozoan, Paramecium multimicronucleatum, is sensitive and responsive to a cooling stimulus. We found that inhibitors of prostaglandin (PG) biosynthesis reduced the response to the cooling stimulus. Inversely, the response suppressed by the inhibitors was recovered by application of stable PGI(2) analogs, including iloprost. Paranecium cells showed binding activity specific for [H-3]iloprost. Moreover, an arachidonic acid metabolite, possibly PGI(2), was rapidly increased in response to the cooling stimulus, suggesting that prostaglandin biosynthesis plays a crucial role in the cooling-sensory transduction, Paramecium may be a useful model for the investigation of the molecular basis of thermo-sensory mechanisms.