The adverse effects of antidepressant medication are now well documented. However, the effect on the immune system following treatment with such drugs has not been fully elucidated and many reports contain inconclusive and sometimes conflicting findings. We have examined the potential immunotoxicity of imipramine in rats following a single dose. Imipramine at 100 mg/kg, but not at 10 or 50 mg/kg, significantly decreased body weight gain and relative weights of the spleen and thymus gland in rats, as compared to controls, 3 days after administration. Histopathology of the spleen and thymus revealed lymphodepletion in the cortex of the thymus and a reduction in the white pulp of the spleen, which are regarded as typical signs of an immunotoxic insult. The peripheral white blood cell count did not alter. However, the evidence from organ weight data and histopathology indicates that imipramine may have some immunotoxic properties.