A number of cyclic and linear somatostatin (SRIF) analogs have now been found to have promising levels of selectivity for rodent somatostatin receptors (rsst2,3,5), but not sst1 and sst4. Comparisons between binding affinities for these and transfected human receptors are just beginning to emerge and we present results from a comparison of affinities of several key families of peptides for sst2 present on rat AR42J cells and on cells transfected with human (h)sst2. The typical cyclic octapeptide analogs, octreotide, lanreotide, and RC-160, exhibited similar affinities to SRIF for rsst2, but somewhat lower affinities for the human receptor. Affinities of several analogs for transfected hsst5 were also measured. As with the rat receptor, octreotide-related analogs had low affinity for hsst5. The highly specific rsst5 analog, DC-23-99, was less so for the human receptor; however, a D-Tyr1 version of DC-23-99 had subnanomolar affinity (Ki, 0.68 nmol/L) and high selectivity. A new extended-ring analog, BIM-23268D, showed superior affinity to DC-23-99 and even to SRIF and SRIF-28 for hsst5 (K(i), 0.38 nmol/L), and had the highest sst5/sst2 selectivity ratio of any analog that we have tested thus far.