Abstract Somatostatin (SS) and its analogs exert inhibitory effects on secretive and proliferative processes of various cells via high affinity SS receptors (SS-R). SS analogs bind with different affinity to the five cloned SS-R subtypes. Octreotide, an octapeptide SS analog, binds with high affinity to the SS-R subtype 2 (sst2). SS-R have been demonstrated in vivo and in vitro on cells from endocrine and immune systems. Among the lymphatic tissues, the thymus has been shown to contain the highest amount of SS, suggesting a local functional role of the peptide. We investigated the SS distribution and SS-R expression pattern in the normal human thymus using autoradiography, membrane homogenate binding studies, and RT-PCR. In addition, the effect of SS and octreotide on growth of cultured thymic epithelial cells (TEC) was studied. By autoradiography, binding of[ 125I-Tyr0]-SS-28 and[ 125I-Tyr3]-octreotide was detected in all seven thymuses studied. Specific[ 125I-Tyr3]-octreotide binding was shown on membrane preparations from thymuses, while not from cultured thymocytes. RT-PCR showed the expression of sst1, sst2A and sst3 messenger RNA (mRNA) in the thymic tissue, whereas sst1 and sst2A mRNAs were found in isolated TEC. SS mRNA was present in thymic tissue and in isolated TEC. SS and octreotide significantly inhibited 3H-thymidine incorporation in 3 of 3 and 6 of 6 TEC cultures, respectively. The percent inhibition ranged from 38.8 to 66.8% for SS and from 19.1 to 59.5% for octreotide. In conclusion, SS mRNA and sst1, sst2A, and sst3 mRNAs are expressed in the normal human thymus. Cultured TEC selectively express sst1 and sst2A mRNA and respond in vitro to SS and octreotide administration with an inhibition of cell proliferation. These data suggest a paracrine/autocrine role of SS and its receptors in the regulation of cell growth in thymic microenvironment.