The effect of the antimalarial drug mefloquine on human neutrophil degranulation, chemiluminescence, superoxide production and viability was examined in vitro. Mefloquine was found to significantly stimulate the release of lysozyme, β-glucuronidase and myeloperoxide at a concentration of 10 μg/ml (2.5 × 10^––5<i>M</i>) without loss of cell viability. At 40 μg/ml mefloquine (1 × 10^––4<i>M</i>) cell viability was significantly decreased. Mefloquine at 10 μg/ml also significantly increased the release of lysozyme and β-glucuronidase but not myeloperoxidase when neutrophils were stimulated with opsonized zymosan. At a lower zymosan concentration myeloperoxidase release was also increased. Enzyme activity was not directly stimulated by mefloquine. Mefloquine at 10 μg/ml significantly increased luminol-dependent chemiluminescence but significantly inhibited lucigenin-dependent chemiluminescence when neutrophils were stimulated with opsonized zymosan. Under these conditions superoxide release, measured by cytochrome c reduction, was inhibited to a lesser degree. These results are discussed with reference to our previous report that mefloquine inhibits the neutrophil iodination reaction [Immunology <i>58</i>: 125–130, 1986] and the use of mefloquine as an anti-inflammatory drug.