Somatostatin is known to modulate mesangial and tubular cell function and growth, but the somatostatin receptor (sst) subtypes responsible for these effects have not been defined. There are at least five different sst receptor subtypes (sst(1)-sst(5)). We used RT-PCR to demonstrate that normal human kidney consistently expresses mRNA for sst(1) and sst(2) (9 of 9 donors). Some donors expressed sst(4) or sst(5) mRNA, but none expressed sst(3) mRNA. Expression of sst(1) and sst(2) was further assessed by staining serial sections of normal human kidney with sst(1) and sst(2) antisera, Arachis hypogaea (AH) lectin (to define distal tubule/collecting duct cells), Phaseolus vulgaris lectin (proximal tubules), and Tamm-Horsfall protein (THP) antiserum (thick ascending limb of the loop of Henle). Specificity of antisera was demonstrated by transfection and absorption studies. Sst(2), but not sst(1), was expressed in glomeruli. Intense sst(1) and sst(2) staining localized exclusively to AH+ and THP+ tubules. Thus sst(1) and sst(2) subtype-selective analogs may be useful to beneficially modulate renal cell function in pathological conditions.