The status of the blood-brain barrier (BBB) was examined following short-term forced swimming (FS) exercise in younger rats (age 8-9 wks, 80-90 g). Subjection of animals to continuous FS for 30 min duration increased the permeability of the BBB to Evans blue albumin (EBA) and 131I-sodium in 5 and 8 brain regions, respectively. Extravasation of the tracers was markedly pronounced in the cerebellum followed by the cerebral cortex. EBA staining was confined mainly to the posterior cingulate cortex, parietal and occipital cortices, whole cerebellar vermis and the mediolateral cerebellar cortices as well as the dorsal surface of the hippocampus. In addition to the above brain regions. BBB permeability to 131I-sodium extended to the caudate nucleus, thalamus and hypothalamus. At this time period, the serotonin (5-hydroxytryptamine, 5-HT) content showed a profound increase in plasma and brain of about 150% and 250% respectively from the control value. Pretreatment with p-CPA (p-chlorophenylalanine, a serotonin synthesis inhibitor) prevented both the increased permeability of the BBB and the rise in plasma and brain 5-HT level. However, prior treatment with cyproheptadine (a 5-HT2 receptor antagonist) prevented the increased permeability alone. The 5-HT level continued to remain high. These results suggest that short-term FS increases BBB permeability in specific brain regions. This increased permeability appears to be mediated through serotonin via 5-HT2 receptors.