We studied the effects of TNF-alpha or GM-CSF on the production of reactive oxygen species (as measured by chemiluminescence) and degranulation responses of neutrophils to opsonized inflammatory microcrystals. TNF-alpha in the 10-2000 pM or GM-CSF in the 2-200 pM concentration range caused the concentration-dependent amplification of neutrophil chemiluminescence responses to both calcium pyrophosphate dihydrate (CPPD) and monosodium urate monohydrate (MSUM) crystals. Degranulation responses, as measured by the extracellular release of the granule enzymes myeloperoxidase or lysozyme, were amplified by approximately 50-100% for both MSUM or CPPD crystal-induced neutrophil activation when cells were pretreated with TNF-alpha at 2000 pM or GM-CSF at 75 pM.