In vitro experiments on vascular smooth muscle often fail to reveal phenomena clearly demonstrable in vivo. Several recent observations in our laboratory have revealed the facility to uncover responses mediated by receptors whose functional expression had remained hidden with the standard experimental conditions first employed: conversely manipulation of conditions can selectively hide a particular receptor’s response. Examples include the uncovering of responses to: 5HT<sub>1</sub> receptors by raised O<sub>2</sub> tension (via cyclooxygenase products) in human umbilical vessels; α<sub>2</sub>-adrenoceptors in rabbit saphenous artery by angiotensin II and α<sub>2</sub>-adrenoceptors in perfused rat tail by elevating tone with vasopressin. The powerful synergism of agonists which cannot on their own cause contraction, can lead to inaccurate interpretations of agonist-antagonist interactions. Finally, the influence of tissue metabolism on receptor expression clearly illustrates the complex processes which must be involved in vivo.