The aim of our study was to induce changes in the plasma elimination half-life (t(1/2)(elim)), rate and extent of urinary excretion, and biodistribution of a model macromolecule, poly-L-lysine, in rats following complexation with heparin. Male Sprague-Dawley rats were dosed intravenously with either unfractionated [(3)H]heparin, FITC-labelled poly-L-lysine, or an [(3)H]heparin:FITC-labelled poly-L-lysine complex. Serum and blood concentration vs time and urinary excretion profiles were determined as well as the resulting patterns of biodistribution to liver, spleen, kidney, and muscle tissue. While the mean values for the total body clearance of poly-L-lysine and the complex were not significantly different, the volume of distribution and the half-life associated with elimination from the serum were increased greater than 2-fold for the complex compared with free poly-L-lysine. The rate and extent of elimination in the urine followed the relative rank order; heparin > poly-L-lysine> heparin:poly-L-lysine complex. Thirty minutes following intravenous administration, there was significantly more tissue deposition/uptake of the complex in the liver, kidney, and muscle, but not the spleen, when compared with poly-L-lysine administered alone. Complexation of heparin to poly-L-lysine effectively increased the fraction of an administered dose of poly-L-lysine that was deposited in liver, kidney, and muscle tissue. Due to the macromolecular complex being nontoxic and uncharged, potentially it might serve as a suitable carrier for both conventional and peptidic drugs to increase drug distribution to liver, kidney, or muscle tissue.