The five cloned somatostatin (SRIF) receptors (ssts) are presumed to subserve unique biological roles by virtue of their tissue-specific expression and particular signal transduction mechanisms. However, the function of any individual sst subtype in its normal physiological milieu is not understood, because tissues and cells often express multiple ssts and, in the absence of receptor-specific SRIF analogs, the actions of individual receptors cannot be identified. To unravel the physiological role and signaling mechanism of the ssts, we have generated receptor subtype-specific antibodies and used these antibodies to determine the distribution of the receptor proteins and to identify the signal-transducing molecules with which particular sst subtypes interact.