Phenyl saligenin phosphate (PSP) induces a characteristic neuropathy (OPIDN), the molecular basis of which has not been precisely defined. This study examined the in vitro effects of PSP on the phosphorylation of serine and threonine residues of proteins in porcine brain cytosol. Quantitative analysis of Western blots probed with antibodies recognizing phosphorylated serine residues demonstrated that 100μM PSP induced a significant increase in the phosphorylation of serine residues of a 50kDa protein. This protein was identified as the α- and β-tubulin subunits by probing Western blots of extracts separated by two-dimensional polyacrylamide gel electrophoresis with anti-phosphoserine and anti-tubulin antibodies. By contrast, threonine phosphorylation of the 50kDa polypeptide and other proteins detected on Western blots probed with anti-phosphothreonine antibodies, was not significantly affected by PSP. These data indicate that PSP is able to induce increased phosphorylation of tubulin in serine residues, consistent with a possible role for this phenomenon in OPIDN induction.