Developing human fetal salivary glands of gestational age from 10 to 40 weeks (n = 100) and normal adult glands (n = 10) were examined for immunoreactivity to S-100 protein and its subunits S-100 alpha, S-100 beta, glial fibrillary acidic protein (GFAP) and neuron specific enolase (NSE). In the early intermediate developmental stage (19-32 weeks) some acinar basal cells showed immunoreactivity to S-100 protein which rapidly disappeared in the late developmental stage (33-40 weeks). Adult salivary glands were negative for S-100 protein. The S-100 alpha subunit was strongly positive in the glandular ducts and acini of both fetal and adult glands. The S-100 beta, although present in some acini and ductal cells during the late intermediate developmental stage, was rarely seen in the adult glands. GFAP and NSE was positive at the developing salivary epithelium in the early developmental stage (15-18 weeks). The above findings indicated that the developing salivary epithelia showed transient appearance of the neuronal phenotype during active cytodifferentiation stage of glandular acini and ducts. Therefore, after evaluation of normal developmental and neoplastic transformation of the salivary glands a suggestion that neuronal differentiation of ductal reserve cells is responsible for the production of modified myoepithelial cells in both normal developmental salivary gland and neoplastic transformation is made.