A 31-year-old woman manifested significant emotional symptoms and personality change due to neurosyphilis; her clinical symptoms were improved with quantitative penicillin treatment. On admission, magnetic resonance imaging (MRI) showed no abnormal findings, while N-isopropyl-p-[123I] iodoamphetamine single photon emission computed tomography (123I-IMP SPECT) initially showed a remarkable increase in cerebral blood flow (CBF) in the cerebral cortex. This increase disappeared after improvement of the patient's clinical symptoms with treatment. It appears that the increase in CBF might have reflected an active inflammatory state of neurosyphilis and that its disappearance might therefore represent successful treatment with penicillin for neurosyphilis. Our case study suggests that single photon emission computed tomography (SPECT) is a useful method for evaluating an inflammatory state and for assessing the effect of therapy on neurosyphilis.