<i>Background:</i> The nature of the aging process has been the subject of considerable speculation. It has been reported that in the aging process several components of the signal transduction pathways, including phosphoinositide, protein kinase C, protein kinase A and reactive oxygen intermediate (ROI) generation, are altered. <i>Objective:</i> The aim of our study was to evaluate the functional metabolic balance among cAMP, cGMP and ROI generation by human neutrophils in relation to age. <i>Methods:</i> The age-induced ROI generation was studied in healthy subjects ranging in age from 20 to 80 years old, divided into 6 age groups: 20–29, 30–39, 40–49, 50–59, 60–69 and 70–80 years old. The oxidizing cellular generation was quantified in a luminol-dependent (ROI production) chemiluminescence assay and the results expressed as relative light units per minute. <i>Results:</i> Our results show a differential functional metabolic balance of cAMP and cGMP in relation to age from 50 years on. This phenomenon is reflected by the increase in ROI generation by neutrophil stimulation with cGMP at all ages and a simultaneous lack of effect of cAMP on cGMP from 50 years old. The same results were observed when neutrophil reacted with endogenous contents of cGMP (levamisole, an inhibitor of cGMP phosphodiesterase) or cAMP (aminophylline, an inhibitor of cAMP phosphodiesterase). Our results show that the lack of modulation of the endogenous or exogenous contents of cAMP or cGMP on ROI generation altered the age-related functional metabolic balance. <i>Conclusions:</i> This altered functional metabolic balance in cAMP, cGMP and ROI generation of neutrophils may certainly have consequences on host defenses, mainly on inflammatory processes, in healthy subjects from 50 years old. However, the exact consequences of this phenomenon on the aging process remain unknown.