N-acetylcysteine (NAC) enhances the release of histamine induced by the fluoride-calcium system but not by compound 48/80. After preincubation of the cells for 2 h at room temperature (RT) as well as at 37 degrees C, NAC was found to enhance histamine release also when induced by compound 48/80. Both fluoride treatment and prolonged incubation at 37 degrees C (but not at RT) for 2 h decreased the ATP content of the cells. NAC was found to counteract the fall in ATP caused by prolonged incubation of the cells at 37 degrees C but not when induced by exposure to sodium fluoride. The results do not favor the concept that free radicals generated by fluoride treatment are responsible for the subsequent sensitivity of the cells to the secretory action of calcium. On the other hand, it cannot be excluded that free radicals generated during prolonged incubation of the cells at 37 degrees C might be involved in the decrease of the sensitivity of the cells to the secretory action of the fluoride-calcium system and of compound 48/80. This is supported by the finding that the presence of NAC not only activated the secretory response but also counteracted the decrease of the cellular ATP content noted following preincubation of the cells for 2 h at 37 degrees C.