Exposure of young rats (9-10 weeks) to chronic summer heat (36 degrees C) or acute heat (38 degrees C, 4 hr) increased the permeability of the blood-brain barrier (BBB) to Evans blue albumin complex and [131I]sodium in different regions of the brain, which correlated well with the increased level of 5-hydroxytryptamine (5-HT) in plasma and brain. This increased permeability of the blood-brain barrier and the increased level of 5-HT were prevented by pretreatment with para-chlorophenylalanine (p-CPA), indomethacin and diazepam. Pretreatment with cyproheptadine and vinblastine, however, prevented only the increased permeability of the blood-brain barrier; the plasma and level of 5-HT in brain continued to remain high. These results indicate a probable role of 5-HT as one of the factors leading to the increased permeability of the blood-brain barrier in young rats following heat stress.