In order to explain the difference in susceptibility to Fasciola hepatica and F. gigantica between animal species, the activity of their excretory-secretory products (FhESP and FgESP, respectively) on concanavalin A (ConA)-induced proliferation of different animal species (sheep, mouse and buffalo) lymphocytes was compared. At high doses, FhESP inhibited proliferation of lymphocytes of all the animal species tested, and at low doses they inhibited the proliferation of sheep lymphocytes and increased the proliferation of buffalo and mouse lymphocytes. The effects of FgESP were similar but the intensity of FgESP inhibition was less than FhESP. The immunomodulatory effects of FhESP or FgESP could not alone explain the susceptibility level of hosts to Fasciola spp. The immunomodulatory molecules of FhESP and FgESP and their role in the course of Fasciola spp. infection should be further investigated.