Single isolated lobules from term placentae were bilaterally perfused with Earle's solution, and the release of human chorionic somatomammotrophin (HCS) was measured by radioimmunoassay. HCS was secreted almost exclusively to the maternal side. Concentrations released at the beginning of perfusions were quite similar to established maternal blood values (up to 10 microgram HCS/ml). Secretion then continued for at least 3 hours at a fairly linear rate. Acetylcholine, a prominent constituent of the noninnervated human placenta, and other cholinergic drugs failed to alter this pattern of hormone output in both intact lobules and dynamically superfused placental fragments. The ability of the placenta to respond to alterations in the perfusion environment was verified by stimulating the HCS secretion with 1 mM dibutyryl cyclic adenosine monophosphate and by modifying calcium concentrations. High calcium (10 mM CaCl2) led to a sustained increase of HCS release.