The effects of chronic treatment with the non-sedative histamine H1 receptor antagonist terfenadine (5 mg/kg, i.p.) for 16 days on some behavioural and immunological parameters were studied in the olfactory bulbectomized (OB) rat model of depression. In the open field apparatus, OB rats showed a significant increase in ambulation and rearing scores. Following terfenadine treatment, this hyperactivity was significantly attenuated. In untreated OB rats, neutrophils phagocytosis and lymphocyte proliferation were significantly suppressed. Terfenadine administration markedly reversed the suppression of these immunological parameters in the treated OB animals, but did not reverse the abnormalities in the differential white blood cell count caused by bulbectomy. These results suggest that the histamine H1 receptor antagonist terfenadine may have antidepressant properties and that terfenadine is effective in reversing some of behavioural and immune changes in the olfactory bulbectomized rat model of depression.