Thyroxine (T4) administration to adult female mice significantly increases submandibular gland (SMG) nerve growth factor (NGF) and epidermal growth factor (EGF) concentrations and does so in a time- and dose-dependent manner. Postnatal maturation of the SMG can be markedly accelerated by T4 treatment. We, therefore, performed a series of experiments to examine the effect of T4 on SMG NGF and EGF content and concentration as a function of postnatal age in neonatal mice. In experiment 1, male and female neonatal Swiss-Webster mice received daily subcutaneous injections of T4 (0.4 micrograms/g body weight) for 6, 13, or 20 days and were sacrificed 24 h after the last injection. Vehicle injected mice served as controls. SMG NGF and EGF content and concentration were measured by specific double antibody radioimmunoassay systems. Pools were made using either female or male SMGs. Since no significant differences were noted for NGF or EGF content using sex of the animal as the determining variable, the values were combined. At 7 days of age, mean SMG NGF and EGF content and concentration of control mice significantly exceeded those of T4-treated animals (p less than 0.05). At 14 days of age, mean SMG NGF and EGF content in T4-treated mice significantly exceeded those in control mice by 39- and 22-fold, respectively (p less than 0.001). At 21 days of age, these increases were 4100- and 2400-fold, respectively. In order to determine more precisely the time of onset of responsivity of the SMG to thyroid hormones, a second series of experiments was performed.(ABSTRACT TRUNCATED AT 250 WORDS)