Exposure of conscious young rats to 4 h heat stress at 38 degrees C in B.O.D. incubator was associated with increased blood-brain barrier (BBB) permeability in 14 brain regions studied. In the same regions cerebral flow (CBF) diminished by 4-65%, but the magnitude of flow reduction was not correlated with the degree of increased BBB permeability. On the other hand, a correlation was observed with increased plasma and brain 5-hydroxytryptamine (5-HT) levels. p-Chlorophenylalanine (p-CPA), indomethacin and diazepam pretreatment prevented both the increased BBB permeability and 5-HT levels following heat exposure. Whereas cyproheptadine and vinblastine pretreatment prevented the increased BBB permeability alone. The probable mechanism(s) underlying the BBB permeability is discussed.