Chronic neurodegeneration in the brains of Alzheimer’s disease (AD) patients may be mediated, at least in part, by the ability of amyloid beta (Aβ) to exacerbate inflammatory pathways in a conformation-dependent manner. In this regard, we previously reported that the Aβ-peptide-mediated potentiation of inflammatory cytokine secretion from interleukin-1β (IL-1β)-stimulated human astrocytoma cells was conformation dependent. Other amyloidogenic peptides, such as human amylin, which display similar conformation-dependent neurotoxic effects, may also elicit inflammatory cytokine secretion from glial cells. To test this hypothesis, we compared human and rat amylin for the effects on cytokine production in U-373 MG human astrocytoma cells. Human amylin alone stimulated U-373 MG cells to secrete IL-6 and IL-8 in a concentration-dependent manner with maximum effects seen at 10–25 μ M peptide. In addition, human amylin markedly potentiated IL-1β-stimulated cytokine production with a similar concentration dependence. In contrast, nonamyloidogenic rat amylin modestly stimulated cytokine secretion, either alone or combined with IL-1β. Aging human amylin resulted in diminished cytokine secretion, probably due to the formation of large, less active aggregates. In agreement with our previous studies using Aβ, extracellular Ca<sup>2+</sup> was necessary for human amylin stimulation of cytokine secretion. Our data suggest that amyloidogenic peptides promote cytokine secretion through similar β-sheeted secondary-structure- and extracellular-Ca<sup>2+</sup>-dependent mechanisms.