Clinical conditions such as hemolytic anemias and certain neuromuscular diseases in which serum hemopexin levels are either increased or decreased were simulated in rhesus monkeys by administering heme intravenously daily at three dose levels over a period of 10 days. At the lower dose of heme (0.02 to 0.04 mg/kg/day), serum hemopexin levels were elevated to 150% of control (control = 53.3 +/- 2.8 U/100 ml). At the higher dose of heme (5.0 mg/kg/day), hemopexin levels decreased to 60% of control. After an intermediate dose of heme (0.6 mg/kg/day), no change was seen in the circulating hemopexin levels. These changes appeared to be specific for hemopexin, since neither the serum haptoglobin levels nor the transferrin level was affected by the heme administration at any of the dose levels. Parameters of hemopexin metabolism revealed that after administration of the low dose of heme there was a 76% increase in the net rate of hemopexin synthesis, resulting in a 65% increase in the intravascular pool size of hemopexin. At the intermediate dose there was a 43% increase in the rate of hemopexin synthesis accompanied by a 33% increase in catabolism, resulting in no net change in serum hemopexin concentrations. At the high dose of heme there was a 57% increase in catabolism of hemopexin without a concurrent increase in synthesis, resulting in lowered circulating hemopexin levels. These findings seem to indicate a relationship between the amount of heme presented to the liver and net hemopexin synthesis.