Six normal subjects received synthetic substance P intravenously in successively increasing doses of 0.5, 1.0, 2.0, 4.0, and 8.0 pmol X kg-1 X min-1. Each dose was given for 20 min. Concentrations of substance P in plasma and infusions were measured radioimmunochemically. The incremental plasma concentration of substance P correlated linearly to the dose infused. Metabolic clearance rate was 0.361 X kg-1 X min-1, and the half-life of exogenous substance P 1.6 min. Lacrimation and sustained flushing were elicited at plasma concentrations above normal range. Transient flushing in spite of continued infusion was seen at 'physiological' levels. Pulse rate and blood pressure did not change significantly.