Hypothalamic temperature-sensitive neurons have a pivotal role in body temperature regulation. To study their thermal transduction mechanism, we made nystatin-perforated patch-clamp recordings from warm-responsive (WR) and cold-responsive (CR) neurons in rat hypothalamic slices after blocking synaptic transmission in low Ca2+ high Mg2+ solution. Warming depolarized the WR neurons and increased their firing frequency, whereas the same procedure suppressed firing in CR neurons. Warming increased the voltage-gated sodium and potassium currents and the input conductance in both types of neuron. The warm-activated current in WR neurons had a reversal potential that was significantly more positive than that of CR neurons. We suggest that the different thermosensitivity of resting ionic conductances underlie the differential behaviours of WR and CR neurons.