Comparison of the physiologic responses in rabbits to the intravenous infusion of two polymorphonuclear neutrophil (PMN) activators, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate (PMA), has revealed marked differences in kinetics for activation between these agents. FMLP infusion was associated with maximally increased respiratory rates (RR), a maximally decreased mean blood pressure (MBP), and a maximally decreased absolute granulocyte count (AGC), all within the first 5 min after infusion. However, there were no significant differences between RR, MBP, and AGC of FMLP-treated animals and controls, 15 min postinfusion and after. On the other hand, PMA did not cause significant changes in RR or MBP until 30 min and 2 h postinfusion, respectively. Previous work has demonstrated that both FMLP and PMA stimulate the PMN metabolically in vitro via the same respiratory burst enzyme, NADPH oxidase, but that each of these activators demonstrates kinetics which are different from the other. Thus, these data from an in vivo study support previous in vitro findings and offer further evidence that the neutropenia and cardiopulmonary alterations following intravenous infusion of FMLP and PMA may be caused by metabolic activation of the blood PMN.