Research over the past 5 years has demonstrated that immunologic activation of mouse macrophages induces the activity of nitric oxide synthase, which oxidizes a guanidino nitrogen of L-arginine, yielding citrulline and the reactive radical, nitric oxide. A review of the biochemistry and immunologic regulation of this pathway in macrophages provides a backdrop against which to evaluate its effector functions. Reports published in the past 2 years suggest that synthesis of NO mediates much of the antimicrobial activity of mouse macrophages against some fungal, helminthic, protozoal and bacterial pathogens.