Rats were treated with injections of diazepam (1 or 10 mg/kg) and stressed by restraint lasting 3 hours. This was performed once or, in animals immunized with sheep erythrocytes, repeatedly for 4 consecutive days. After repeated stress and/or diazepam treatment, the levels of brain noradrenalin decreased in all treated groups. Although both treatments (stress and diazepam) diminished the 5-hydroxytryptamine (5-HT)/5-hydroxyindoleacetic acid (5-HIAA) ratio, treatment with either dose of diazepam prevented the stress-induced fall of this ratio. The activity of hypothalamic glutamate decarboxylase, the enzyme taking part in GABA synthesis, was affected neither by the acute nor by repeated stress and/or diazepam treatment. The levels of plasma corticosterone were enhanced in all stressed rats, with and without drug. This finding was in accordance with the enhanced weights of adrenal glands in repeatedly stressed rats. The tendency to a corticosterone rise after repeated treatment with diazepam, 10 mg/kg, coincided with the enhanced weights of adrenal glands in these animals. The plaque-forming cell (PFC) response was reduced in all stressed animals and in animals treated with diazepam, 10 mg/kg. Accordingly, high doses of diazepam given repeatedly to rats are immunosuppressive, achieving this effect presumably by an enhancement of glucocorticoid secretion. Neither the low nor the high doses of diazepam affect the stress-induced enhancement of hypothalamohypophysial-adrenal axis activity and consecutive immunosuppression.