The granular convoluted tubule cells of the mouse submandibular gland contain high concentrations of nerve growth factor (NGF) and epidermal growth factor (EGF). Levels of the two growth factors increase in parallel during development and after stimulation by thyroid hormone, androgens, and glucocorticoids, suggesting that similar controls regulate the production of both proteins. At the same time, however, the granular convoluted tubules hypertrophy, with resulting increases in glandular size and protein content. In this study, we have monitored changes in salivary concentrations of NGF and EGF in the absence of detectable changes in submandibular size or protein concentration. Both growth factors exhibited identical diurnal changes, peaking between 1200-2000 h. In addition, after secretagogue-stimulated release of the proteins into saliva, reaccumulation began after 2 h, with normal levels of both molecules attained 6 h posttreatment. These data indicate that submandibular NGF and EGF can be controlled by similar cellular or molecular mechanisms independent of the regulation of generalized growth responses.