The immunomodulatory activity of an Indian Ayurvedic medicinal preparation, Ashwagandna (Withania somnifera (L. Dunal)) was studied in mice with myelosuppression induced by one or more of the following three compounds: cyclophosphamide, azathioprin, or prednisolone. The assessment of immunomodulatory activity was carried out by hematological and serological tests. A significant modulation of immune reactivity was observed in all the three animal models used. Ashwagandha prevented myelosuppression in mice treated with all three immunosuppressive drugs tested. A significant increase in hemoglobin concentration (P < 0.01), red blood cell count (P < 0.01), white blood cell count (P < 0.05), platelet count (P < 0.01), and body weight (P < 0.05) was observed in Ashwagandha-treated mice as compared with untreated (control) mice. We also report an immunostimulatory activity: treatment with Ashwagandha was accompanied by significant increases in hemolytic antibody responses towards human erythrocytes.