Humoral and cellular immune responses to Fasciola hepatica excretory-secretory products (ESPs) in primary and secondary experimental infections in goats were studied. Primary infection induced the development of chronic subclinical fascioliasis that did not affect the establishment of flukes coming from the secondary infection, as the same percentages of recovered flukes were found in both groups. The specific IgG response to F. hepatica ESPs was similar in primary and secondary infections; challenge flukes did not induce any modification in the IgG response. The specific lymphocyte response to F. hepatica ESPs was absent in most of the infected goats, both primarily and secondarily infected. A modulation of the nonspecific cellular responses to mitogens was also observed. All infected goats showed a reduced proliferative response to concanavalin A and phytohemagglutinin. According to our results, humoral and cellular responses to F. hepatica ESPs in goats have no protective effect on the establishment of flukes and the development of disease in either primary or secondary infections.