Nitric oxide (NO) appears to be an important and pleiotropic bioregulator of immune responses. The existence of the NO synthase (NOS) pathway in human monocytes/macrophages remains a subject of controversy, despite an increasing number of reports suggesting that human monocytes produce NO in vitro in response to various stimuli. Here, Bernard Dugas and colleagues consider the arguments supporting these conclusions, with particular emphasis on the results obtained by ligation of the low-affinity IgE receptor (Fcepsilon RIIb/CD23b).