We studied plasma lipoprotein and hormone concentrations in rhesus monkeys that had consumed either a low protein (3.8% of kilocalories) or a control protein (13.9%) purified diet since birth (6-10 yr before the beginning of this experiment) in order to test the hypothesis that chronic protein deficiency could influence plasma lipoproteins through an effect on the hepatic metabolism of gonadal or thyroid hormones. Protein-deficient monkeys had greater plasma concentrations of very low density lipoproteins (VLDL) plus high density lipoproteins (HDL) than controls. They also had lower serum albumin and greater alkaline phosphatase levels than the controls. Plasma thyroxine (T4) and free T4 concentrations were lower and the triiodothyronine (T3) levels tended to be greater in the protein-deficient group than in controls. This effect was apparent at two widely different levels of dietary iodide. Plasma T3 concentrations were elevated in other adult rhesus monkeys that were fed the low protein diet for only 6 wk. Monkeys injected with estradiol benzoate (100 micrograms/kg body weight) for 4 d had a marked reduction of VLDL concentrations. VLDL triglycerides were depressed more and plasma estrone levels were greater in deficient monkeys than in controls at 24 h after the last injection. In the control monkeys the T3 level rose and T4/T3 fell in response to estrogen injections, whereas the deficient monkeys did not respond.