The effect of subacute intracerebroventricular (icv 0.1, 0.5, and 1.0 microgram) administration of corticotropin-releasing factor (CRF) for 5 days on behavior, neurotransmitter concentrations, and immune functions was studied in rats. The results showed that CRF administration produced a dose-dependent increase in locomotor activity in the "open field" test compared with controls; rearing scores were also significantly increased. In the elevated plus maze apparatus, rats given 1.0 microgram CRF spent considerably less time on the open arms when compared with controls. Following 0.5 and 1.0 microgram of CRF infusion, the concentrations of noradrenaline (NA), dopamine (DA) and 5-hydroxy indole acetic acid (5-HIAA) were significantly increased in the hypothalamus. There was no significant change in the concentrations of neurotransmitters in the other brain regions. CRF administration also produced a dose-dependent increase in the levels of corticosterone in the serum. The immunological results clearly showed that subacute icv CRF administration caused a reduction of lymphocyte proliferation, a decrease in the percentage of lymphocytes, and an increase in neutrophil percentage in the differential white blood cell (WBC) count, a decrease in neutrophil phagocytosis, and elevated leucocyte adhesiveness/aggregation (LAA) compared with control animals. These results suggest that icv subacute administration of CRF has anxiogenic effects, increases biogenic amine concentrations in the hypothalamus, and changes in some aspects of immune functions that may reflect the stress-inducing properties of the peptide. These effects are time and dose dependent.