Immunocytochemistry with antibodies against cytoskeletal proteins has been used to search for molecular differences in the spinal cord from patients with motor neuron disease (MND) of amyotrophic lateral sclerosis type and normal spinal cord. Monoclonal antibodies which recognize phosphorylated neurofilament epitopes diffusely labelled a proportion of normal and MND anterior horn cells, but did not permit differentiation between normal and MND tissue. However, in some MND and control anterior horn cells, dense 'floccular' accumulations were labelled by antibodies recognizing phosphorylated neurofilament epitopes. These accumulations of phosphorylated neurofilaments suggest abnormalities of cytoskeletal regulation, but were neither a common nor a specific feature of MND. Axonal spheroids, which were as common in normal as in MND tissue, were labelled by all antineurofilament antibodies. Normal-appearing axons, but not spheroids, in MND and control tissue were identified by an antiactin antibody, indicating that actin may be absent from the cytoplasmic domain which gives rise to spheroids. In summary, we have not found specific posttranslational changes of cytoskeletal proteins in MND and, in particular, phosphorylated neurofilament epitopes are common to both MND and control anterior horn cells.