The binding of 125I-human growth hormone (125I-hGH) to membranes from female and male rat brain was studied. The binding was time-, pH- and protein concentration-dependent. The binding capacities calculated for the hormone were higher in the female brain (12.1 fmol/mg protein) than in the male brain (4.5 fmol/mg protein). In the female brain, saturation isotherms yielded dissociation constants (Kd) of 6.2 x 10(-10) and 4.5 x 10(-8) M and maximal binding (Bmax) of 2.9 and 8.4 fmol/mg protein for the high and low affinity binding sites, respectively, and in the male brain a Kd of 2.3 x 10(-9) M and a Bmax of 3.5 fmol/mg protein. Displacement studies indicated that in the female brain the binding of 125I-hGH was inhibited in a dose-dependent manner more potently by lactogenic than by somatogenic hormones. The rank order of potencies of these hormones to inhibit the binding of 125I-hGH was hGH > hPRL > rPRL > oGH > rGH. However, in the male brain the inhibition of 125I-hGH binding was found to be most pronounced by somatogenic hormones with the rank order of hGH > oGH > rGH > hPRL > rPRL. These findings indicate the presence of specific binding sites for hGH in the rat brain. The level as well as the properties of these sites vary in the two sexes, with higher levels in the female brain as compared to the male brain. Moreover, these sites display predominantly lactogenic characteristics in the female brain and almost exclusively somatogenic characteristics in the male brain.