The pineal gland plays an important role in seasonal adaptation including variation in energy requirement. Animals exhibiting seasonal changes in their energy expenditure would be benefited if their cardiac and pulmonary systems respond to the pineal photoperiodic signal, melatonin, appropriately. Thus, we would like to hypothesize that melatonin receptors are present in the heart and lung. Using a specific labeled melatonin agonist, 2-[125I]iodomelatonin, binding sites were demonstrated in the lung and heart of birds and other animals. In the chicken lung, there were high affinity (equilibrium dissociation constant, Kd = 9.11 +/- 0.73 pmol/l) and low density (maximum number of binding sites, Bmax = 1.29 +/- 0.16 fmol/mg protein) 2-[125I]iodomelatonin binding sites that were highly specific to melatonin. Similar binding with lower density was demonstrated in the quail and frog lungs. In the duck heart, specific 2-[125I]iodomelatonin binding sites with a Kd of 30.5 +/- 3.5 pmol/l and a Bmax of 0.46 +/- 0.1 fmol/mg protein (n = 4) were demonstrated. Competitive studies suggested that these binding sites were specific to melatonin. Thus, saturable and reversible 2-[125I]iodomelatonin binding was present in the lung and heart membrane preparations of birds and possibly other animals. The picomolar affinity, femtomolar density and highly specific pharmacological profile of these binding sites suggest that they can be classified as ML-1 melatonin receptors. The 2-[125I]iodomelatonin binding sites described in the lung and heart as well as those binding sites demonstrated in other peripheral tissues suggest the ubiquitous direct action of melatonin on peripheral tissues.