Immunization of piglets with two different European-type modified live vaccines against porcine reproductive and respiratory syndrome (PRRS) virus produced different outcomes. After vaccination, pigs became viremic (42 days), neutralizing antibodies did not develop, and frequencies of virus-specific gamma-interferon-secreting cells (IFN-gamma-SC) were low. Levels of interleukin-10 (IL-10) produced by peripheral blood mononuclear cells (PBMC) seemed to inversely correlate with interferon-gamma responses. After a challenge with a virulent Spanish strain, one vaccine (V3) protected piglets against viremia while the other (V1) did not. The vaccine V3 induced the highest IFN-gamma-SC frequencies. IL-2, IL-4 or transforming growth factor-beta responses were not detected at any time for neither of the vaccines. In contrast, haptoglobin rose in sera of viremic pigs after the challenge. These results indicated a strong involvement of IFN-gamma, and maybe IL-10, in the development of immunity against PRRS virus.