Brief exposure of Escherichia coli, Serratia marcescens, Klebsiella pneumoniae and Salmonella typhimurium to supra-inhibitory concentrations of aztreonam enhanced their susceptibility to phagocytic killing by human polymorphonuclear leucocytes. The effect was independent of the continuous presence of the antibiotic and required the presence of serum opsonins. Phagocytic killing of Pseudomonas aeruginosa was enhanced by prior exposure to subminimal inhibitory concentrations, and killing, relative to control bacteria, was not increased with increasing concentrations of aztreonam above minimal inhibitory concentrations. The degree of sensitization, and the range of bacteria susceptible to antibiotic modulation varied between antibiotics. Under the conditions of these experiments, gentamicin sensitized pseudomonas, but failed to sensitize E. coli, while cefotaxime failed to sensitize serratia, and varied in it's activity against E. coli and pseudomonas. Enhanced killing of aztreonam-pretreated bacteria was associated with an increase in uptake by leucocytes. Aztreonam exposure decreased the liability of the bacteria to hydrophilic interactions in an aqueous two-phase partitioning system. These observations indicate that exposure of Gramnegative bacteria to aztreonam enhances phagocytic killing through modification of cell surface structures. This may be mediated through an increase in surface hydrophobicity which enhances bacterial association with leucocyte membranes with subsequent phagocytosis and intracellular killing.