Area postrema neurons mediate various autonomic responses, including emesis. We examined the effects of propofol, a widely used anesthetic with antiemetic properties, on the hyperpolarization-activated cation current (Ih) in rat area postrema neurons using a slice patch-clamp technique. Although propofol suppressed Ih of area postrema neurons in a dose-dependent manner that was similar to what we observed for the hippocampal CA1 neurons, the IC50 for Ih in area postrema neurons (38 microM) was more than six times less than that found for hippocampal CA1 neurons (235 microM). We conclude that rat area postrema neurons are exquisitely sensitive to propofol. Given that reductions of Ih are associated with decreased excitability in neurons, we believe that the known antiemetic effects of propofol anesthesia are at least partly a result of a direct action on area postrema neurons to lower their excitability.