The understanding and importance of antigen-specific immune responses after vaccination has completely changed in recent years. In the past, the focus for monitoring a vaccine-specific immune reaction was principally on the humoral branch of the immune system. The efficacy of vaccines, as assessed by the induction of protective immunity was mainly correlated with antibodies and antibody-titers. However, this correlation often failed and other parts of the immune system had also to be considered: namely, the innate immune system and the cellular branch of the antigen-specific immune system. With regard to vaccines, the innate immune system plays its main role in the effective activation of the antigen-specific immune response, in antigen-uptake and antigen-presentation. The dendritic cells (DCs) are the most important antigen presenting cells which present processed protein antigens (peptides) through MHC-molecules: MHC-class I, for the presentation of endogenous synthesised antigen; MHC-class II for exogenous antigen. Activation of DC leads to an enhanced production of cytokines and chemokines, to an up-regulation of co-stimulatory and activation molecules and also molecules for cell-cell interactions, e.g. interactions with cells of the antigen-specific immune system. T lymphocytes are the effector cells of the cellular branch of the antigen-specific immune system. They act either as MHC-class I-restricted cytolytic T lymphocytes (CTL) or as MHC-class II-restricted T-helper cells providing support for B lymphocytes (T(H)2) and the cellular part of the antigen-specific immune system (T(H)1). In order to achieve effective vaccination, the activation of all T-cell subpopulations is of advantage, but more important is the generation of antigen-specific memory T and B lymphocytes. In addition to these 'generic' immunological factors which are essential for the design of more efficacious vaccines, our detailed knowledge about feline and canine immune reactions after vaccination, which is still poor, has to be improved.