Intracutaneous injection of histamine acid phosphate (HAP) and salivary gland extract (SGE) of Haemaphysalis spinigera and Rhipicephalus sanguineus sanguineus into sensitized and nonsensitized rabbits previously injected intravenously with Evans blue indicated that the ticks' saliva contained a pharmacodynamic substance in addition to having antigenic properties. A primary skin reaction in nonsensitized rabbits produced by this pharmacodynamic substance within 30 min was amplified by a more extensive skin reaction in sensitized rabbits. It was postulated that, in concert with this pharmacodynamic component of the ticks' saliva, a histamine-blocking agent detected in the salivary gland of R. s. sanguineus would provide an efficient mechanism for regulating the quantity of tissue fluid available for the engorging tick, while simultaneously neutralizing the deleterious effects of excess pharmacodynamic substance in the host's tissues.