We characterized the presence of opioid peptide receptor sites in plasma membranes and cells from human midterm and term placentas. Incubations with [3H]ethylketocyclazocine (EKC) at increasing doses revealed the presence of high affinity, low capacity, opioid peptide receptor-specific binding of the K-type. Scatchard analysis of the binding data showed, in the plasma membranes, linear plots at both stages of pregnancy with similar mean equilibrium association constants of 1.31 ± 0.29 (±se) × 109 mol/L−1 (n = 4) at midterm and 0.52 ± 0.63 × 109 mol/L−1 at term (n = 4). In placental cells (n = 4) from term gestations, the binding plots were curvilinear; the first component had a Ka of 5.51 ± 0.50 × 109 mol/L−1, and the second component had a Ka of 1.33 ± 0.81 × 108 mol/L−1 (P < 0.01). When standardized per mg tissue protein, the number of binding sites in plasma membranes increased from 13.8 ± 9.8 fmol at midterm to 50.0 ± 18.6 fmoi at term (P < 0.05). For term placental cells, the concentration of binding sites was 81.2 ± 36.0 fmol for the high affinity sites and 713 ± 390 fmol for the lower affinity sites. Specificity for the κ-type of OPR was found based on the inability of μ-or δ-opioid peptides, as well as LHRH and TRH, to compete for [3H]EKC binding. Term placental cells incubated with various doses of opioid peptides had a 50% increase in placental lactogen production. The increase was significantly higher than controls only with κ-agonists (P < 0.05), maximal with 10−9 mol/L EKC, and completely inhibited by 5 × 10−6 mol/L naloxone. These results expand on previous data demonstrating the presence of opioid peptide receptor in placental plasma membranes and suggest a role for opioid peptides in regulating secretion of placental lactogen by placental cells.