Polymorphonuclear leukocyte function and lymphocyte blastogenesis in response to mitogens were evaluated in castrated male cattle after the repeated administration of estradiol or progesterone. Polymorphonuclear leukocyte function was evaluated with the following five parameters: (i) random migration under agarose, (ii) ingestion of 125I-labeled Staphylococcus aureus, (iii) nitroblue tetrazolium reduction, (iv) iodination, and (v) antibody-dependent cell-mediated cytotoxicity. The administration of high dosages of estradiol cypionate produced no measurable effect on the total or differential leukocyte count, neutrophil function, lymphocyte blastogenesis, or blood cortisol levels. The administration of high dosages of progesterone caused a significant enhancement of random migration by neutrophils and a depression of the activity of the myeloperoxidase-H2O2-halide antibacterial system (iodination) of the neutrophil. Progesterone administration did not cause a measurable effect on the lymphocyte blastogenic response to mitogens or the ability of polymorphonuclear leukocytes to ingest S. aureus, reduce nitroblue tetrazolium, or mediate antibody-dependent cell-mediated cytotoxicity. Progesterone did not cause a change in blood cortisol concentrations; therefore, the observed effects on polymorphonuclear leukocyte function were not due to alterations in blood cortisol concentrations. Impairment of the iodination reaction indicates that high dosages of progesterone interfere with an important bactericidal mechanism of the neutrophil.