Although pronounced changes in astrocytes and microglia accompany the neuronal degeneration observed in a murine model of familial amyotrophic lateral sclerosis, the significance of non-neuronal cell contribution to the disease process remains unclear. Activated astrocytes and microglia are capable of secreting numerous cytokines, some of which may have potentially harmful effects on neuron survival. For this reason we wished to determine the expression pattern of various cytokines in the spinal cords of transgenic mice expressing a Cu-Zn superoxide dismutase mutation (Tgn G93A SOD1) by using semi-quantitative RT-PCR. Three different patterns of cytokine expression were observed in G93A SOD1 transgenic mice. For most cytokines, we were unable to detect mRNA expression in Tgn G93A SOD1 mouse spinal cords at any age, yet message was readily detected in spleen or activated splenocytes. A second pattern, typified by TNF-alpha, was characterized by mRNA expression prior to the onset of motor deficits and increasing until the terminal stages of the disease. For other cytokines, including TGF-beta1 and M-CSF, mRNA expression was detected in young presymptomatic Tgn G93A SOD1 mice (as well as wild-type and transgenic mice expressing wild-type SOD1 (Tgn SOD1)), with upregulation later occurring only in G93A SOD1 transgenic mice. These results indicate a temporal correlation between the expression of certain cytokines and the onset of motor dysfunction in Tgn G93A SOD1 mice and suggest a potential role for these molecules in the disease.