To test the hypothesis that the therapeutic effects of glycosaminoglycan polysulfate (GAP) in primary degenerative dementia of the Alzheimer type (PDD) is associated with a reversal of biochemical changes seen in PDD, a two-phase, clinical-biochemical study was conducted. In the first phase of this study a number of biochemical parameters were compared in 12 patients with PDD and their sex- and age-matched controls, and it was found that platelet monamine oxidase B activity was significantly higher and cerebrospinal fluid (CSF) homovanillic acid levels significantly lower in the PDD than in the normal control group. In the second phase of this study the same 12 PDD patients were treated with GAP at a daily dosage of 250 lipasemic-releasing units for a period of 1 month and it was found that all four biochemical parameters shifted towards normal values during therapy with the changes in CSF 5-hydroxy-indole acetic acid levels attaining statistical significance. Although clinical changes were minimal, in light of prior clinical findings in studies conducted with GAP in similar populations, the possibility was entertained that clinical improvement with GAP in PDD patients is preceded by biochemical changes.