The production of prostaglandins has been studied in neonate rat primary mixed glial cultures. A correlation was found between inhibition of [3H]thymidine incorporation in the cultures and production of prostaglandin, which was stimulated by the addition of supernatant from Con A-activated rat splenocytes. Inhibition of prostaglandin synthesis in the cultures by indomethacin results in a striking increase in incorporation of [3H]thymidine into the cultures, an effect which was reversed by the addition of exogenous PGE2, but not PGF2 alpha. PGE was the principal prostaglandin detected, with both macrophages/microglia and astrocytes contributing to the output. A possible role for prostaglandins in the modulation of inflammatory responses in the central nervous system is discussed.