Our previous studies suggest a central nervous system regulatory center that adjusts the brain's convulsive response to the insulin hypoglycemia based on decreased sensitivity to insulin hypoglycemic convulsions 24 hr after a single i.p. injection of gold thioglucose (GTG). This decrease is a change in the convulsive response to equal hypoglycemia and is not a change in the generalized convulsive threshold. GTG simultaneously causes a cytotoxic lesion focused in the ventromedial-arcuate hypothalamus (VMH), and the proposed regulatory center may be thought of as a "GTG-lesioned glucostat." However, 5-thioglucose (5TG) substitutes for GTG in decreasing the sensitivity to insulin hypoglycemic convulsions but does not lesion the VMH. In the present study, two possible explanations were explored for this previously reported dissociation of the 5TG functional effect and the VMH lesion. First, an interaction of 5TG with the GTG-lesioned glucostat in the VMH, without itself causing a lesion, was not supported by competition experiments, i.e., GTG lesion formation was not inhibited by appropriate 5-TG pretreatment. beta-D-Thioglucose, for which the sulfur substitution is more like GTG, is also compared. Two indices of GTG lesion formation were used, histology and the increased body weight that eventually results from a VMH lesion. Second, no 5-TG-induced lesion was found anywhere in the brain. Thus, no support was found for the possibility that 5-TG and GTG share a common lesion at some site other than the main VMH lesion of GTG. Other explanations must be sought.