A radioimmunoassay for monkey placental lactogen (MPL) was developed to study the factors controlling the secretion of MPL. The sensitivity of the assay was 1 ng MPL per ml. Human and monkey growth hormone, and human placental lactogen (HPL) showed minimal cross-reactions with MPL. Maternal MPL concentrations as measured in 40 rhesus monkeys increased progressively throughout pregnancy to a mean of 5000 ng/ml at term while umbilical vein MPL was less than 50 ng/ml. After term delivery maternal MPL concentrations decreased rapidly with a t½ of 20 min.After fetectomy but with retention of the placenta, MPL concentrations decreased by 25% reaching a plateau over a 6 hr period. Experimental abruption of the secondary placenta within 1 hr produced a 50% decrease in MPL concentration. After ligation of the fetal vessels supplying the secondary placental disc, MPL increased transiently and then decreased to levels significantly below those of the control period.These studies suggest MPL secretion is not directly controlled by the fetus but is sensitive to changes in placental blood flow. The pregnant rhesus monkey serves as a useful model for investigating factors which may regulate HPL secretion because of the close similarity between MPL and HPL secretion.