Clotrimazole (CLT), clinically used as an antifungal drug, inhibited sponge-induced angiogenesis and granulation tissue metabolic activity when administered systemically (120 mg/kg) in rats. We have used functional, biochemical and histological parameters to assess neovascularization and fibrovascular tissue infiltration of the rat sponge granuloma. The sequential development of local blood flow as determined by the outflow rate of sodium fluorescein applied intraimplant, showed that the t1/2 values for the fluorescence peak in the bloodstream decreased in the control group from an initial value of 11 +/- 0.87 min (avascular implants, day 1) to 7.6 +/- 1.5 min at day 7 postimplantation. By contrast t1/2 values in the CLT-treated group remained stable during the 7-day period. The hemoglobin content extracted from the control implants was 2.7 +/- 0.14 microgramsHb/w.w vs. 1.8 +/- 0.18 microgramsHb/w.w in the treated group. The functional and biochemical parameters correlated well with the histological study. Furthermore, the metabolic activity of the sponge-induced granulomas was inhibited by CLT. Because CLT is an inhibitor of signal transduction interfering with the ionic fluxes across the cell membranes, our results suggest that the onset and maintenance of inflammatory angiogenesis induced by subcutaneous implantation of sponge matrix may be regulated by ionic fluxes.