Early studies suggested that at low temperatures there was a transition of receptor type from an H1to an H2receptor when the temperature was reduced from 37 °C to temperatures below 20 °C. These original observations were based on the development of sensitivity of guinea-pig ileum to the H2antagonist metiamide as the temperature was reduced. More recently, evidence from a number of laboratories has cast doubt on the existence of a simple H1–H2receptor transition, but there is abundant evidence that there are major changes in the response of a variety of smooth muscle preparations to histamine at reduced temperatures. The evidence in regard to alterations in histamine response at low temperatures is reviewed, some new evidence presented, and a model which is consistent with most of the observations is suggested.