We investigated the effects of prostaglandin (PG) E1 on the hypoxic injury of fetal rat hippocampal cells. Primary hippocampal cell cultures (embryonic day 18) were established and maintained. After 72 h in culture, PGE1 was added to the serum-free medium at a final concentration of 10(-5)-10(-9) M. Cultures were divided into two groups: The normoxia group was in culture for another 48 h, and the hypoxia group was exposed to 24 h of hypoxia followed by continuation of culture for another 24 h. As a quantitative measure of cell death, lactate dehydrogenase (LDH) activity was estimated in the culture medium. The LDH activity, released by the hypoxic insult, was significantly smaller with PGE1 treatment at 10(-6), 10(-7), and 10(-8) M (p < 0.01) and 10(-9) M (p < 0.05) compared with the control. No differences in the LDH activities were observed in the normoxia group. Glial culture was not affected by the hypoxia. Western blot analysis showed an increased induction of 62-kDa c-Fos and 58, 60, and 66 kDa Myc proteins in rat hippocampal cells with 10(-7) M PGE1 treatment. We conclude that PGE1 at concentrations of 10(-6)-10(-9) M protects rat hippocampal neurons against hypoxic insult.