We present a study of the random scission process of polymers, in which numerical simulations are combined with experimental investigations into the acid hydrolysis of the polysaccharide hyaluronan (HA), in particular at pH 1.1 and SO C. As input for the simulations, an initial molecular weight distribution (MD(0)) and the hydrolysis rate constant (k(h)) are needed. The first was obtained using agarose gel electrophoresis followed by densitometric analyses, by which we determined the evolution of the full molar-mass distribution during hydrolysis. The rate constant was experimentally obtained by two independent techniques. Kinetic plots were obtained from both the number- and the weight-average molar mass (M-n and M-w, respectively), converted to degrees of polymerization (N-n and N-w, respectively), and from these, k(h) values for HA hydrolysis were derived. For confirmation, k(h) was also determined from the evolution of the concentration of reducing chain ends. Experimentally determined k(h) values were used as input for the model, and the evolution of MD during hydrolysis was simulated for various hypothetical MD(0) functions as well as for an experimentally determined MD(0) curve. Agreement between experimental and simulated results demonstrated consistency of the model and indicates that acid hydrolysis of hyaluronan can indeed be considered a random scission process. We show that for cases where the initial molar mass distribution is not of the Kuhn-type-which is often the case the value for the k(h) determined from the evolution of Mn is more accurate than that obtained from M-w.