Helicobacter pylori causes chronic gastritis punctuated with fluctuating episodes of acute distress that can lead to peptic ulcer disease. Several factors produced by the bacterium have been shown to initiate the inflammatory response, but mechanisms potentially involved in the down-regulation of inflammation have not been described. We show that nitric oxide (NO) released from synthetic NO generators causes a rapid and dose-dependent morphologic conversion of H. pylori from the replicating spiral form to the nonreplicating, but viable, coccoid form. Because only spiral organisms—and not coccoid forms—are capable of inducing interleukin-8 secretion by epithelial cells, this conversion could result in down-regulation of the inflammatory response. These data suggest that the increase in NO synthase activity observed during gastritis results in morphologic conversion to a potentially dormant but viable H. pylori.