A study was made to characterize the effects of living Trypanosoma brucei brucei and its products on prostaglandin D2 (PGD2) and PGE2 production by fibroblasts and astrocytes. Cultured fibroblasts were prepared from Microtus agrestis embryos and astrocyte cultures were prepared from neonatal rats. The cultures were maintained in low-endotoxin or defined media (i.e. endotoxin-free). The PG production was compared with and studied in combination with a defined lipopolysaccharide (LPS) from Escherichia coli. Living T. b. brucei were without effect on PG production. Preparations of T. b. brucei prepared by freeze-thawing and sonication produced dose- and time-dependent increases in PGD2 and PGE2 synthesis by both cell types. LPS caused a similar pattern of increases. The combination of parasite products with LPS caused synergistic production to levels higher than the maximal production by each mitogen alone. The findings have important implications for several pathological features that accompany trypanosomiasis.