The responses to diazepam (DZ) and phenobarbital (PhB) were studied in enriched neuronal primary cultures from rat embryo hemispheres. Cells were grown in chemically defined medium and the drugs were added for 3 days to cultures, at pharmacologically active concentrations. Following exposure to DZ or to PhB, morphological changes, such as less prominent neuronal processes, were observed in neurons. It was also shown that each drug reduced the specific uptake of 2-deoxy-D-glucose by the cells and interfered with protein and RNA metabolism. It was concluded that both DZ and PhB might affect, at least transiently, the normal growth of neurons in culture.