Summary—Endothelin‐1 (ET‐1) by itself was not an effective stimulus for inducing superoxide (O2*) generation in human resting or DMSO‐differentiated neutrophil‐like HL‐60 cells. ET‐1 (0.01 – 100 nM) was not able to modulate O2* generation stimulated by the chemotactic peptide N‐formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine (fMLP, EC50= 4.24 ± 1.63 nM in the absence and 3.16 ± 1.95 nM in the presence of ET‐1). Neither did ET‐1 (0.01 – 100 nM) promote the mobilization of intracellular calcium ions or modulate fMLP‐induced [Ca2+]iincrease in this model of human neutrophils. Phosphoramidon, a neutral endopeptidase inhibitor, was not able to reveal any biological (O2*) or biochemical ([Ca2+]i) response to ET‐1 in the absence or in the presence of fMLP in these cells. These results indicate that DMSO‐differentiated neutrophil‐like HL‐60 cells are not sensitive to ET‐