We have previously demonstrated in a rat surgical incision model that charged dextran beads enhance wound repair in a charge-specific manner: positively charged beads increased wound breaking strength (WBS), whereas neutral or negatively charged beads were ineffective. The present work extends these observations into two models of radiation-impaired healing. One hundred five rats were divided into three groups: group 1, controls, no irradiation; group 2, total body irradiation; group 3, surface irradiation. Three days after irradiation, 0.1 ml of a suspension of either positively charged beads, neutral beads, or vehicle alone was applied to paired 6-cm incisions on the dorsum of the rats. Ten days later, wounds were excised and sample strips were harvested for determination of WBS and for histological analysis. Following total body irradiation, positively charged beads enhanced WBS 84% compared to beadless controls. When results with positively charged beads were compared to those with neutral beads, a 39% increase in WBS was noted. Healing, as measured by WBS, was more impaired in surface-irradiated animals, but when results with positively charged beads were compared with those obtained with neutral beads, a similar degree of healing (+38%) was noted. Neutral beads proved ineffective. Histology revealed that neutral beads evoked a modest foreign body response, yet there was a consistently greater clustering of giant cells around positively charged beads in wound sites. This paralleled in vitro experiments demonstrating increased monocyte aggregation around positively charged beads in tissue culture. The results suggest that positively charged ion exchangers, such as these positively charged beads, perhaps through their recruitment and/or activation of wound macrophages, may have a potential clinical role in the treatment of impaired wounds.