Immunity to Babesia infection depends on the innate resistance of the host in addition to specific responsiveness to babesial antigens. Activated macrophages and their soluble products (monokines) are effective in stimulating nonspecific immunity to babesiosis. Specific immune mechanisms include both humoral and cellular components. Protective antibodies induced primarily as a result of helper T lymphocyte activity neutralize merozoite invasion of erythrocytes and enhance phagocytosis of free parasites and infected cells. There is now good evidence that recovery from Babesia infections is T lymphocyte-dependent, with natural killer cells also playing a role in protective immune responses. Exoantigen-containing supernatant fluids from Babesia in vitro cultures are now being used as soluble immunogens for vaccination against bovine babesiosis and are efficacious in the induction of heterologous strain immunity in susceptible cattle.