Clinical observations during infection suggest that in aged patients, the kinetic or proliferative responses of neutrophils to infection may be deranged. To test this hypothesis, the neutrophil responses of 6-month-old and 30-month-old mice were compared. After intrapulmonary injection of Escherichia coli, young mice exhibited neutrophilia and diminution of the neutrophil storage pool (NSP) by a mean of 6.4 x 10(6) neutrophils/two femurs. This was accompanied by an increase in the pool of CFU-GM from a control value of 1.1 x 10(5) cells/two femurs (range 0.7 to 1.4) to 1.5 x 10(5) (1.1 to 1.9) (P less than .05) and the thymidine suicide (relative proliferative rate) of CFU-GM rose from 27% (19 to 42) to 51% (31 to 61) (P less than .05). Furthermore, the CFU-GM of infected young mice displayed enhanced differentiation to the neutrophil series. In contrast, old mice exhibited a greater mean diminution of the NSP: 12.8 x 10(6) neutrophils. Also, old mice experienced a reduction in CFU-GM from 2.3 x 10(5) (1.0 to 3.9) (controls) to 1.3 x 10(5) (1.2 to 1.5)/two femurs (P less than .05), a reduction in the proliferation of CFU-GM and reduced differentiation of CFU-GM to neutrophils. These experiments establish that the neutrophil response of infected old mice is disordered, with exaggerated depletion of the NSP and lack of stimulus-driven granulocytopoiesis as reflected by a paradoxical reduction in the number and proliferative rate of precursors. This defect may be compounded by decreased differentiation of precursors to neutrophils.