The concentrations in plasma of the biologically active endogenous peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) have not been measured during development or in female rats. By radioimmunoassay, we found that Tyr-MIF-1 -like immunoreactivity (Tyr-MIF-1-LI) was first consistently detectable in plasma when the rat was 5 days old, and then gradually increased to adult concentrations by day 15. In male rats, the levels remained relatively constant for the next 21 months. In female rats, plasma concentrations of Tyr-MIF-l-LI at day 15 were about the same as in male rats. At 6 months of age, however, the concentrations in females decreased by half and by 21 months of life were only about a third of the concentrations found at day 15 or in age-matched males. The differences with age were not due to the length of time of storage of the samples, because another group of rats 1 month old was killed on the same day as 5-day-old rats and still showed several times more Tyr-MIF-1-LI in the plasma; again, no differences were found between male and female rats at either 5 days or 1 month. A single injection of estradiol followed by progesterone lowered the concentrations in 1-month-old male rats. In female rats that were either ovariectomized or sham-ovariectomized, the expected similarity in their plasma concentrations of Tyr-MIF-1-LI was found at 1 month of age. By contrast, at 2 and 12 months of age, ovariectomized rats had several times more Tyr-MIF-1-LI in their plasma than the sham operated female controls, as would be seen in male rats. The results indicate a significant interaction of sex with age in concentrations of Tyr-MIF-l-LI in the plasma of rats.