Two cardiac glycosides, with different physiochemical properties, were investigated to assess their binding characteristics to filters. The lipophilic cardiac glycoside, digoxin, demonstrated significant (10%) retention to certain cellulose filters. There were considerable differences in the amount of digoxin retained among the cellulose type filters. The polycarbonate type filter (10 microns thick) demonstrated less than 2% retention. This was similar in magnitude to the cellulose-acetate-nitrate ester filters (100 microns thick) which demonstrated less than 1% retention. Ouabain, the polar cardiac glycoside, appeared to have minimal (2%) retention on all filter types tested. Increasing the size of the pore from .4 microM to .8 microM resulted in a minimal decrease in retention for the Amicon filters, whereas the nucleopore polycarbonate filters demonstrated a significant reduction in retention of the lipophilic cardiac glycoside. A comparison of the 100 micron thick filters with the 10 micron thick filters suggests that there is no correlation with the thickness of the filter and the retention of the drug bound by that filter. These studies suggest that lipophilic drugs are retained on membrane filters depending on the filter's composition and that caution should be utilized with the filtration technique.