Oral administration of prednisolone (in single doses of 10, 30, or 60 mg) to healthy volunteers was found to affect the T lymphocytes in the blood with regard to binding of monoclonal antibodies and lactate dehydrogenase isoenzyme pattern. The findings indicate that these effects are dependent on the dose of the drug and the time after the administration of the drug. Prednisolone induces a T lymphocytopenia in the peripheral blood that affects OKT4-positive lymphocytes more than OKT8-positive lymphocytes, resulting in a slight decrease in the ratio OKT4/OKT8. Moreover, the lactate dehydrogenase isoenzyme pattern changes, resulting in a decrease of the H/M ratio of this enzyme. The proliferative responses of peripheral blood lymphocytes are not affected after a single dose of 10 mg. However, after administration of either 30 or 60 mg of prednisolone, the proliferative responses are decreased to a different extent, depending on the stimulus used. In vitro experiments are presented showing that any effect of prednisolone on nonstimulated lymphocytes is reversible. Based on the observed changes in OKT pattern and lactate dehydrogenase isoenzyme profile of the T lymphocytes induced by administration of prednisolone, it is concluded that the drug induces a temporary depletion from the peripheral blood, preferentially of high-reactive T lymphocytes. As a consequence, the peripheral blood compartment is enriched for T lymphocytes with a low H/M ratio of lactate dehydrogenase isoenzymes, known to be less reactive to proliferative stimuli.