The aim of this study was to determine the contribution of various IgG subclasses to the scintigraphic detection of a staphylococcal infection. An experimental thigh infection in mice was used to determine the accumulation of the various 99Tcm-labelled IgG preparations with enriched IgG1, IgG2 or IgG4 subclass. Multiple-regression analysis was used to investigate a relationship between the IgG subclasses and the time-dependent accumulation in infected sites. Eighteen hours after infection with Staphylococcus aureus bacteria 20 micrograms of 99Tcm-labelled IgG preparations enriched with one of the IgG1, IgG2 or IgG4 subclasses by thiophilic absorption were administered intravenously and target-to-nontarget (T/NT) ratios were determined at 15 min, 1 h, 4 h and 24 h after injection of the tracer. Moreover, the binding of these preparations to S. aureus was assessed using an in vitro bacterial pellet model as an indication for the potency of detecting infections. As a control agent, 99Tcm-labelled polyclonal IgG (HIG) was used. In vivo, the T/NT ratios were significantly (P < 0.05) higher for the IgG1-enriched preparation at all time points, and for the IgG2-enriched preparation at 4 h and 24 h after injection, compared with HIG. In contrast, IgG4 did not yield higher T/NT ratios at any time. Using multiple-regression analysis, it became evident that IgG3 at all time intervals, IgG1 for early scans (up to 4 h) and IgG2 for late scans (24 h) contribute significantly (P < 0.05) to the accumulation. The abundance of IgG subclasses in the various preparations appeared to influence the accumulation of tracer at infected sites. The percentage of binding to S. aureus in vitro was significantly (P < 0.05) higher for enriched IgG subclass preparations than for HIG. We conclude that specific subclass enrichment of 99Tcm-labelled IgG preparations improves the scintigraphic detection of staphylococcal infections at various time intervals post-injection.