We recently introduced a freeze-fracture replica labeling method adapted to studies of bacterial envelopes. This report describes a further development of this detergent-digested freeze-fracture replica labeling technique, thus more exactly the conception of this explicit methodology for visualization of bacteria-host cell interactions. Our experimental model employs human neutrophils and the gastric pathogenic bacterium Helicobacter pylori. The phagocytic process performed by the neutrophils represents a crucial element of the host defense system against invading microorganisms, and by so doing, it allows direct observation of the interplay between bacteria and host cells at an ultrastructural level. The here launched methodology can be used as a tool to investigate the events taking place between pathogenic microbes and phagocytes, as well as for pinpoint targeting of other cell-cell communications in the field of cell biology.