Neutrophils, treated with sequential additions of bacterial products such as endotoxin (E. Coli lipopolysaccharide, LPS) and the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP), undergo to metabolic activation and express membrane-anchoring proteins that promote adhesion to serum-coated culture wells. By investigating the dose-response relationships of these phenomena, we have found that: (a) resting neutrophils do not produce a significant amount of superoxide (0;) and show only minimal adhesion to serum-coated plastic surfaces; (b) fully activatory doses (> 5 x ~O-*M) of fMLP induce the release of 0; and a significant increase of the cell adhesion; (c) pretreatment of the cells for 1 h with LPS augments cell adhesion to serum-coated culture wells in the absence of further stimulation and primes the neutrophils to enhanced fMLP-dependent 0; release; (d) addition of low, substimulatory doses of fMLP (from 10-I'~ to 5 x 1 0 -9 ~) inhibits and reverses the adhesion of LPS-treated cells, (e) high fMLP doses (> 1 0 -7 ~) are additive to LPS in promoting adhesion. Phorbol-myristate acetate (> 1 0 -9 ~) increased adhesion in both normal and LPS-treated neutrophils, but low doses of this stimulant did not inhibit adhesion. Low doses (10-9~) of fMLP increased intracellular cyclic AMP in both normal and LPS-treated neutrophils, suggesting that stimulus-induced rises in CAMP may be the negative signal responsible for down-modulation of adhesion. Low (5 x 1 0 -9 ~) and high (5 x 1 0 -7 ~) fMLP doses induced the same increase of expression of CDI ljCDl8 integrins, indicating that the inhibition of adhesion caused by low doses is not due to quantitative down-regulation of integrins. These findings may provide an in vitro model of the complex biological events involved in the regulation of neutrophil adhesion.