Nonpeptidyl agonists for the somatostatin (SRIF) receptor family have been developed. We have studied the desensitization effects for two of these agonists upon SRIF receptor function in AtT-20 cells, a neuroendocrine tumor cell, which endogenously expresses two distinct SRIF receptor, subtypes. We observe that SRIF and the nonpeptidyl, subtype selective agonists, differentially regulate SRIF receptor subtypes in the AtT-20 cell.