Previous work by other authors has shown that alloxan-induced diabetes increases whereas streptozotocin-induced diabetes does not alter nonesterified fatty acid (NEFA) plasma levels. The present study replicates these results and demonstrates that fasted, streptozotocin-induced diabetic animals also have increased NEFA levels. In addition, brain levels of 5-hydroxytryptamine (5-HT) and of its immediate precursor and metabolite were measured. Alloxan- and fasted, streptozotocin-induced diabetic rats showed significant increases in brain indoleamine concentrations, whereas fed, streptozotocin-induced diabetic rats had unchanged levels of the same compounds. Levels of brain indoleamines exhibited a strong positive correlation with wet-dog shakes (an index of 5-HT activity) elicited by hippocampal stimulation. Blockade of wet-dog shakes by 5-HT receptor antagonists strengthens the proposal that this behavior is a good index of central 5-HT activity. The increased content of brain indoleamines in alloxan- and fasted, streptozotocin-induced diabetic rats may be related to the increased NEFA plasma levels seen in the same animals. This hypothesis is supported by the positive correlation demonstrated between NEFA and 5-HT levels. In conclusion, it is suggested that alloxan-induced diabetes may represent a useful model for studying the various behavioral changes known to occur in diabetics.