To determine whether so-called uraemic toxins exhibit direct toxic effects on Schwann cells, the latter were cultured in a monolayer with the addition of uraemic toxins. Proliferation of Schwann cells was estimated with [H-3]-thymidine incorporation into DNA synthesis. Myoinositol, methylguanidine, guanidinosuccinic acid, parathyroid hormone, phenol, p-cresol, 4-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid were added at various concentrations to the culture medium. Addition of myoinositol at concentrations between 50 and 100-mu-g/ml, values analogous to those in uraemic serum, inhibited proliferation of Schwann cells in a dose-dependent way. Myoinositol also inhibited axolemma-stimulated proliferation of Schwann cells. The other compounds at concentrations occurring in uraemic serum did not show any toxic effect on Schwann cells. These results suggest that myoinositol has a neurotoxic effect on Schwann cells, and uraemic polyneuropathy seemed to be caused by a defect in maintaining normal myelin due to accumulation of myoinositol.