Infection with Leishmania may have different outcomes in genetically distinct individuals and the course of infection is determined by the nature of the host innate and adaptive immune response. Thus in experimentally infected mice, and in naturally infected dogs or humans, the protective (self-healing or asymptomatic) phenotype is associated with the induction of Th1-regulated cell-mediated immunity. By contrast, a Th2-regulated humoral immune response is associated with severe symptomatic disease. In the murine model system there is strong correlation between clinicopathological phenotype and the nature of the antigen-specific humoral immune response. Symptomatic infection and Th2-regulation is associated with elevation in antigen-specific IgG1 and IgE, whereas asymptomatic infection with Th1-regulation is linked with IgG2a production. IgG subclass restriction is less clear in human disease with only some clinical forms being correlated to a specific serological profile. Although numerous studies have questioned whether infected dogs develop skewed IgG subclass usage, the results of these have been conflicting-suggesting bias towards IgG1 or IgG2 or neither subclass in different investigations. This confusion could relate to the specificity of the commercially available polyclonal antisera used to detect the canine IgG1 and IgG2 subclasses. More meaningful results might be obtained by the use of the panel of monoclonal antibodies with well-validated specificity for all four canine IgG subclasses.