During the treatment of four patients with cerebral manifestation of Wilson's disease, we measured the copper concentration in the cerebrospinal fluid (CSF) and serum, the serum coeruloplasmin concentration, the free copper concentration in the serum, and the albumin ratio CSF/serum (AR). These measurements were treated as indicators of the copper-related toxic effects on the brain and the blood-brain barrier (BBB). The half-life of the decrease in the CSF copper concentration during therapy was 23.5 +/- 5.78 months (mean +/- S.E.M.). The therapeutic-target-copper concentration in the CSF (mean normal concentration) is below 20 microg/l. The average length of therapy needed to normalize CSF-copper values in our patients with an average initial value of 76.25 microg/L was 47 month. During the first 10 month of treatment there was an increase in all cases of the measured disturbance in the blood-brain barrier (measured as the ratio of albumin in CSF to albumin in serum, AR). All patients showed an initial worsening of the neurological condition, on average after 1.75 +/- 0.25 months. The maximal rise in AR, from the initial values, was on average 18.4 +/- 5.08%; this maximum was reached after an average of 6.9 +/- 1.5 months. The AR normalized during therapy, indicating a reduction in toxicity in the blood-brain barrier region. The extent of the AR increases in individual patients did not correlate significantly with CSF copper half-life, serum copper half-life, the initial half-life of the reduction in the ratio (copper in serum)/(coeruloplasmin in serum), the initial copper concentration in CSF or serum, the initial free copper concentration in serum, or the initial dose of penicillamine (within the first 2 months). We conclude that the normalization of the CSF copper concentration in patients with the cerebral manifestation of Wilson's disease is a slow process, even if therapy is sufficient. The initial worsening of the neurological condition which has often been reported may be reflected in the disturbance of blood-brain barrier function, which we have measured here for the first time (using the parameter of the albumin ratio CSF/serum). Based on repeated measurements of the AR during the course of treatment it seems that the brain toxicity of mobilized copper can be assessed and the therapy adjusted.