Recent studies have demonstrated the activation of caspase‐1 and caspase‐3 in mice expressing mutant superoxide dismutase 1 (SOD1), models of amyotrophic lateral sclerosis. Caspase‐1 converts the prointerleukin‐1β into a potent proinflammatory molecule involved in the innate immune response and in neurodegenerative diseases. We report on the chronic expression of interleukin‐1β mRNA in the spinal cord of SOD1^G37R mice, together with robust mRNA expression for the nuclear factor‐κB (NF‐κB) inhibitor IκBα, for other proinflammatory cytokines and chemokines (interleukin‐6, tumor necrosis factor‐α, monocyte chemoattractant protein‐1) and for the toll‐like receptor TLR2 involved in innate immunity. To further assess the interleukin‐1β contribution to neurodegeneration, we generated mice expressing SOD1^G37R in a context of interleukin‐1β gene knockout. Surprisingly, the absence of interleukin‐1β had no effect on the life span of SOD1^G37R mice, nor on the extent of motor axon degeneration at age 7 and 10 months. Whereas neither compensatory induction of the interleukin‐1α mRNA nor increases in mRNA levels for IκBα, tumor necrosis factor‐α and macrophage chemoattractant protein‐1 occurred as a result of interleukin‐1β gene disruption, enhanced levels of TLR2 mRNA were detected in SOD1^G37R mice lacking interleukin‐1β. We conclude that interleukin‐1β does not directly contribute to motor neuron degeneration in SOD1^G37R mice, but it may act as a modulator of the innate immune response.