The activity of diamine oxidase, the enzyme that catalyzes the oxidative deamination of putrescine, spermidine, histamine, and other substances involved in the regulation of cell proliferation and immune responses, increases up to 1000-fold in blood of pregnant women. In vivo experiments have shown that progestins stimulate diamine oxidase in the rodent uterus. We examined diamine oxidase activity in human endometrium at different phases of the menstrual cycle and in decidua from first-trimester pregnancies. Enzyme activity was also assayed in tissues and media of cultured human endometrium and decidua in the presence of estradiol or medroxyprogesterone acetate. Enzyme activity in first-trimester decidual tissues (286 +/- 86 mU of diamine oxidase per milligram of DNA; mean +/- SEM) was considerably higher (p less than 0.001) than that in endometrium (2.6 +/- 1.6), and the activity increased from 6 to 17 weeks of pregnancy. No significant differences were detected in proliferative and secretory endometrium. Activities in media of endometrium in organ culture generally were below detectability. Decidua secreted large amounts of the enzyme into the medium (160 to 600 mU per milligram of DNA per day), greatly exceeding the initial tissue activities. Bovine serum, when added to culture media, caused a marked increase in diamine oxidase levels, whereas estradiol (10(-8) mol/L) or medroxyprogesterone acetate (10(-6) mol/L) did not. Kinetic analysis showed a Michaelis constant of 7.4 X 10(-6) mol/L with putrescine as the substrate. Spermidine and histamine were competitive inhibitors of putrescine with an inhibition constant of 1.1 X 10(-4) and 3.5 X 10(-6) mol/L, respectively. These results demonstrate synthesis and export of diamine oxidase by decidua in organ culture, stimulation of activity by serum factors, and competition of histamine, spermidine, and putrescine for the enzyme.