To investigate the mechanism and neural control of the nasal secretion, we observed the isolated rat nasal mucosa by video-enhanced differential interference contrast microscopy. This technique allowed us to visualize abrupt changes of the individual granules leading to degranulation in the acinar cells and in epithelial goblet cells during secretory stimulation. This image provided evidence that exocytosis is the major mode for regulated secretion in the nasal acinar cells and goblet cells. Acetylcholine (ACh, 0.1-100 muM), substance P (SP, 0.1-10 muM), and vasoactive intestinal peptide (VIP, 0.1-1 muM) induced exocytotic responses and shrinkage of the acinus in a concentration-dependent manner. The effects of ACh (10 muM) on the acinus were clearly inhibited by atropine (5 muM), but the effects of SP (1 muM) and VIP (1 muM) were not. The acinar shrinkage always started before exocytosis, suggesting that the fluid secretion precedes the mucus release. In goblet cells, SP (1 muM) and ACh (10 muM) increased the frequency of exocytotic responses significantly, suggesting that these substances truly play the role of a neurotransmitter for nasal secretion. Histamine (HIST) induced no visible response. The effect of HIST on secretory cells may be neuronally mediated in vivo.