The cerebrovascular and metabolic effects of the novel cholinesterase inhibitor eptastigmine were tested in conscious rats. The drug was administered by single intravenous injection, and blood flow or glucose utilization were assessed in 38 brain regions by quantitative autoradiographic techniques. A dose-dependent increase in regional cerebral blood flow (rCBF) was obtained for i.v. doses ranging from 0.5 to 3 mg kg-1. Forty minutes after the dose of 1.5 mg kg-1, average rCBF of the 38 regions studied was (mean +/- SD) 2.62 +/- 0.62 ml g-1 min-1, a value significantly higher than that of saline-injected controls (1.46 +/- 0.26; p < 0.005). In contrast, a similar dose of eptastigmine did not significantly alter regional cerebral glucose utilization (rCGU) (0.90 +/- 0.21 mumol g-1 min-1) when compared with saline-injected controls (0.99 +/- 0.08 mumol g-1 min-1). A linear correlation between rCBF and rCGU was observed both in saline (r = 0.871) and eptastigmine (r = 0.873)-injected animals but the slope of the regression line of rCBF on rCGU was significantly higher (p < 0.01) in the eptastigmine group (2.863 +/- 0.266) than in the controls that received saline (1.00 +/- 0.094). The cerebral vasodilatation induced by eptastigmine peaked at 40 min after drug administration. No toxic signs were observed at the doses used. Mean arterial blood pressure decreased after 0.5 mg kg-1 (control = 109.3 +/- 10.56 mm Hg; eptastigmine = 96.6 +/- 8.10 mm Hg) but did not differ from control at the higher doses. It is concluded that eptastigmine induces a long-lasting increase in rCBF and a significant enhancement of the rCBF:rCGU ratio in most regions. The results suggest an important role of endogenous acetylcholine in the control of cerebral perfusion.