Oral contraception by estrogen/progestogen preparations significantly changed the concentrations of 12 out of 16 immunologically assayed serum proteins. The concentrations of prealbumin, alpha 1-lipoprotein, alpha 1-antitrypsin, ceruloplasmin, alpha 2-SH-glycoprotein, beta 1-lipoprotein, beta 1-A/C-globulin, and transferrin were increased, and those of albumin, alpha 1-glycoprotein, haptoglobin, and immunglobulin A were diminished. The majority of the alterations became apparent after one month of oral contraception and were little affected by further treatment. Age-associated changes, which were found in the controls, were not apparent during oral contraception, with the exception of alpha 2-macroglobulin which was not affected by the contraceptives. The changes in serum proteins produced by oral contraceptives were comparable with those caused by pregnancy, although the latter had more pronounced effects. Estrogen seemed to be responsible for changing the concentrations of albumin, alpha 1-glycoprotein, alpha 1-lipoprotein, alpha 1-antitrypsin, ceruloplasmin, alpha 2-SH-glycoprotein, haptoglobin, transferrin, and immunglobulin A. Prealbumin was influenced by certain progestogens. The changes in plasma proteins were probably caused by increased synthesis of proteins by the liver. No correlation was found between changes in any of the 16 proteins assayed and the results of T3- and T4-tests, thus emphasizing the role of thyroxine binding globulin in carrying the thyroid hormones.