Phagocytic leukocytes such as granulocytes and macrophages form an essential part of human host defense against infection by invading microorganisms. The present study demonstrates that normal fetal granulocytes undergo normal activation (i.e., the transition from the resting state to the respiratory burst) with a 75 +/- 23 sec lag time and generate superoxide at 6.7 +/- 2.3 nmole 02-/min/10(6) cells, a rate similar to that of adult granulocytes. Fetal granulocytes also resemble adult cells in the response of the superoxide generating system to temperature change and to the chemical inhibitors N-ethyl maleimide and 2-deoxyglucose. They show the same pattern of differential effects of these perturbations on the lag time and on the rate of superoxide generation as that previously described for adult granulocytes. The process of activation, expressed as the lag time, shows no inhibition at a high temperature that diminishes by 64% the rate of superoxide production. The metabolic inhibitor 2-deoxyglucose affects only the rate and not the lag time. Both cyanide (in the presence of 2-deoxyglucose) and the sulfhydryl reagent N-ethyl maleimide inhibit the rate equally when added before or after completion of the activation process.