The present study was designed to investigate the ameliorating effects of Cnidiuim monnieri L. Cusson (CM) and osthole, a constituent of CM, on the spatial performance deficit in scopolamine (SCOP)-treated or ovariectomized (OVA) rats. CM improved the deficit of spatial performance, and reversed the lower plasma estradiol levels caused by SCOP in female rats. In addition, osthole (3 and 10 mg/kg, s.c.) improved the performance deficit in OVA rats. It (10 and 30 micrograms/brain, icv) also improved the performance deficit caused by SCOP in intact female rats, and at 30 micrograms/brain improved the deficit in OVA rats. However, osthole did not alter the latency swum to reach the visible target in SCOP-treated and OVA rats. Accordingly, we suggested that osthole is an active constituent of CM, and possesses ameliorating effects on the spatial performance deficits in SCOP-treated female rats or OVA rats. The action mechanism of the effects of osthole on performance deficits was related to the estrogen-like properties and activating the central cholinergic neuronal system.