Sections of the spleen, thymus, lymph nodes and liver, collected from mice at various time intervals after injection with either steroid hormones only, sheep red blood cells (SRBC) only, or SRBC plus steroid hormones, were compared by histological examination. A regimen of 3 injections of 4 mg of cortisol given at 24 hourly intervals was shown to have a more severe effect than 3 injections of 1 mg given at the same times irrespective of whether SRBC were injected or not. The thymic cortex showed rapid and extensive depletion of lymphocytes very soon after corticosteroid treatment and did not recover until about the 8th day. The medulla was affected to a lesser extent. Spleens and lymph nodes showed early lymphocyte destruction, active ingestion of debris by macrophages, and germinal centres were considerably decreased in number and less clearly demarcated in corticosteroid-treated animals than in SRBC immunized controls. Spleens and lymph nodes of mice that received SRBC only exhibited the characteristic morphology of active germinal centre development associated with the immune response. Corticosteroid treatment of mice sensitized with SRBC caused an increase in neutrophilic promyelocytes in bone marrow smears to the 4th day, whereafter their numbers returned to normal. The normoblasts were decreased on the 2nd and 3rd days’ whereafter they increased to normal. Plasma cells were increased in SRBC injected animals in bone marrow smears. Of the effects of the sex steroids studied the most notable was a drastic effect of estradiol on the thymus; both the cortex and medulla were completely depleted of lymphocytes and could hardly be distinguished.