A hypothesis has been developed that ethanol causes adrenergic sub-sensitivity. This has been established in vitro tissue studies, and is supported in vivo by the observation of reduced receptor measured by the plasma cAMP to isoproterenol. First, we will study the mechanism of this reduced receptor sensitivity in vivo to determine if it represents adrenergic subsensitivity. If this is so, it will help to substantiate the adrenergic subsensitivity hypothesis. This will be studied by comparison to in vitro cAMP response to NE. Reduced sensitivity due to ethanol ingestion will be compared with the reduced sensitivity due to reserpinization and isoproterenol. Second, we will study the characteristics of this reduced plasma cAMP response in order to determine the conditions under which it is manifest. This will include dose-response studies and time-course studies to determine the length of time to onset of the reduced cAMP response and its duration. Third, we will study the effect of other agonists upon stimulation of plasma cAMP in ethanol-fed rats. A number of organs will similarly be studied. This will answer the question of which other receptors mediating cAMP production have altered sensitivity due to ethanol, and which organs contain these receptors. This may help to determine which organs are "target organs" for ethanol and why ethanol selectively damages these organs.