Proteins that are immunologically related to human pregnancy-specific beta 1-glycoprotein (hSP1) have been detected in serum samples from pregnant subhuman primates. However, little information is available concerning the concentrations or secretory dynamics of SP1 in nonhuman primate pregnancy. To examine serum SP1 concentrations throughout rhesus monkey gestation, a heterologous RIA for rhesus SP1 (rSP1) was developed which used an antiserum against rSP1 and purified human SP1 as the standard and for iodination. No rSP1 was detected in serum samples from 8 normal male monkeys, 8 castrated females, or 10 regularly cycling females. Levels of rSP1 were measured in 260 serum samples from 43 pregnant monkeys. rSP1 was first detected on day 14 after mating, and all monkeys sampled 25 or more days after mating had detectable serum rSP1 levels. Serum rSP1 rose exponentially from day 14 to about day 50, followed by a more gradual rise until term. This pattern of secretion was in marked contrast to that found for macaque CG, which was already detectable 10 days after mating, peaked at 20 days, and returned to nonpregnant levels by day 40. The disappearance of rSP1 after delivery was best fit by a 2-component 4-parameter model with a mean residence time of 48 h. These data indicate that the pattern of rSP1 secretion throughout pregnancy is qualitatively similar to that found for hSP1, as is the long half-life of the protein in the circulation after delivery. rSP1 measurements may provide a useful index of placental function during rhesus pregnancy and serve as a model to study the biological role of SP1 in primates.