Deficient in vitro functions of neonatal neutrophils have been reported in various species. They may be functionally related to the well-known susceptibility of newborn individuals to microbial infections. To evaluate an early step in the sequence of neutrophil activation, neutrophils from adult cows (A-PMN) and newborn calves (N-PMN) were stimulated with zymosan-activated plasma (ZAP) or with the lipid mediator platelet-activating factor (PAF): Aggregation was recorded kinetically in a standard aggregometer and measured quantitatively as the area under the aggregation curve (AUAC). The mean +/- SEM of the AUAC of the first 2.5 min of the reaction induced with ZAP was similar in N-PMN and A-PMN. However, N-PMN deaggregated only partially, whereas A-PMN deaggregated almost completely (P less than 0.05). This may indicate a mechanism of microvascular sequestration in vivo with the potential to inhibit chemotaxis. PAF (10(-5)-10(-10) M) aggregated N- and A-PMNs similarly and dose-dependently with a maximal reaction at 10(-6) M. Inhibition of aggregation induced by 10(-6) M PAF was evaluated by preincubation with four antiinflammatory drugs: dexamethasone (Dex: 5.1, 51.0, 510.0 microM), flumethasone (Flu: 12.2 and 122.0 microM), phenylbutazone (PB: 0.33 and 3.3 mM), and flunixin meglumine (Flxin: 51 and 510 microM). Dex and Flu each inhibited (P less than 0.05) PAF-induced N-PMN aggregation at the highest dose, and A-PMN aggregation at the two higher doses. PB and Flxin each inhibited aggregation of N- and A-PMNs at all doses used. We compared the inhibition rate in both age groups and could demonstrate that Dex, Flu, and Flxin each at the highest dose, and PB at all doses used, inhibited PAF-induced aggregation less (P less than 0.05) in N-PMNs than in A-PMNs. These functional differences indicate hyperirritability of N-PMNs, and they need further elucidation to help understand mechanisms of increased neonatal susceptibility.