Rhipicephalus appendiculatus salivary glands extracts and saliva contain both biochemically active and pharmacological agents with various effector functions, including inhibition of host enzymes or inactivation of other host molecules that may be important in mounting tick rejection. The majority of these salivary biochemicals may interact with host antibodies at the feeding site or in the gut (or both), that interfere with proper tick attachment and feeding. The possible role of these biochemicals in tick feeding is discussed. Of particular interest is a salivary anticoagulant, which increased as feeding phase progressed and was present in all life cycle stages of the tick. Antibodies raised in rabbits against salivary gland extracts obtained from female if. appendiculatus fed on rabbits for various days, recognized several antigens on Western blots of salivary gland extracts, but failed to react with the purified tick salivary anticoagulant molecule. Thus, tick anticoagulant was poorly immunogenic compared to other salivary moieties. These results may help to explain the strategies adopted by the tick to circumvent biochemical detachment by the damaging host-protective immune responses, thereby enabling the vector to co-exist with its mammalian hosts.