Life-threatening, severely elevated intracranial pressure (ICP) is a common feature of acute liver failure (ALF). Perfusion with a bioartificial liver may serve to mitigate rising ICP. A retrospective analysis of ICP measurements in a canine ALF model prospectively supported with a bioartificial liver support system (BLSS) is presented. Animals are divided into two groups based upon care provided: (i) standard medical care (n = 6); and (ii) standard medical care plus BLSS support (n = 9). Nonparametric analysis with respect to ICP, arterial NH(3), lactate, and supportive-care parameters found BLSS-supported animals evidenced significantly less metabolic acidosis than unsupported animals. Analysis of variance/linear regression for direct dependence of ICP on arterial NH(3), lactate, and supportive care parameters irrespective of care found ICP was uncorrelated with any measured factor (P > 0.06 for all factors). Lack of correlation of ICP with the considered parameters indicates that none of these factors are predictive of the extent of ICP elevation in the D-galactosamine canine model. Blood chemistry and supportive care factors that are correlated with and predictive of ICP elevation remain to be identified.