Specific binding sites for 1 alpha,25 dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] localized to type II pneumocytes have been evidenced in fetal rat lung at the end of gestation, suggesting a role for vitamin D3 in the control of lung maturation. In this study, we describe the morphological changes that occur in lung explants from 18-day-old rat fetuses grown for 1 and 2 days in control conditions and in the presence of 1 alpha,25(OH)2D3 (10(-9) M) or dexamethasone (10(-7) M). Point counting and planimetric measurements on light and electron micrographs show that 1 alpha,25-(OH)2D3 1) dramatically decreases the mean glycogen content of type II cell profiles between days 1 and 2 of the culture, suggesting an acceleration of the glycogenolytic processes normally occurring at that stage and 2) does not change the intracellular osmiophilic lamellar body (OLB) content of cell profiles, but increases the amount of intraluminal surfactant by 126% when expressed as surfactant clusters surface area/section surface area and by 129% when expressed on a per cell basis, suggesting a stimulation of surfactant synthesis and secretion. By contrast, dexamethasone increases the mean intracellular OLB content of type II cell profiles by 306% and decreases the relative surface area of secreted material by 53 and 73%. In conclusion, 1 alpha,25(OH)2D3 accelerates the physiological maturation of fetal rat type II pneumocytes and could represent a key factor for the onset of normal lung function at birth.