The histologic effect of 400 mg/M2/day of hydrocortisone, given alternatively from day 7 to day 19 after birth, was studied on the spleen of the immunologically immature rat. Two days after the cessation of treatment, the periarteriolar lymphatic sheaths were found to be largely depleted of small lymphocytes. Immunoperoxidase studies confirmed a depletion of T lymphocytes. The effects of hydrocortisone on the thymus seem to be more important than its direct lymphocytolytic effect in producing this splenic lesion. In contrast, no apparent change in the number of medium-sized B lymphocytes in the marginal zone was detected. Medium-sized B lymphocytes of the spleen, reported to be responsible for IgM synthesis, appeared to be subjected to a different mechanism of hydrocortisone action, other than lysis, resulting in a decrease in antibody production. Primary follicles were not seen in spleens of hydrocortisone-treated rats. Twenty-three days after treatment, spleens had a histologically normal appearance.

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