Human peripheral blood lymphocytes were incubated in the presence of various concentrations of bovine parathyroid hormone extract (PTH) or with PTH plus different concentrations of plant mitogens (PHA, Con-A and PWM) to determine whether PTH can modulate lymphocyte proliferation. Lymphocyte proliferation was assessed by 3H-thymidine incorporation into the lymphocytes after a 72-96 h incubation period. After initial inhibition, PTH stimulated lymphocyte proliferation at concentrations of 0.25-0.5 micrograms/0.2 ml and inhibited 3H-thymidine uptake at concentrations of greater than 1 microgram/0.2 ml. Similar responses were seen when the lymphocytes were incubated with PTH plus PHA. In contrast, PTH inhibited 3H-thymidine uptake by the lymphocytes when the cells were stimulated with Con-A (0.25-2 micrograms/0.2 ml) and PWM (0.25-2 micrograms/0.2 ml). The suppressive effects of PTH were not due to loss of lymphocyte viability as determined by trypan blue exclusion. It is speculated that the PTH mediated immunomodulatory effect on peripheral blood lymphocytes may be due to PTH itself or to some other factor(s) in the extract. In view of the common embryonic origin of the parathyroid glands and the thymus, the possibility that thymic-like hormones may be involved in the immunomodulatory process cannot be excluded.