Single photon emission computed tomographies (SPECTs) by using N-isopropyl-p-[123I-IMP]-iodo-amphetamine (123I-IMP) and 99mTc-hexamethyl propyleneamine oxime (99mTc-HM-PAO) were serially performed in a 70 yrs. old male with herpes simplex encephalitis (HSE), and the chronological changes of accumulations were studied. Accumulations of both 123I-IMP and 99mTc-HM-PAO increased initially, and then decreased with the stage of HSE being advanced. The sequential appearance of the lesion in HSE with 123I-IMP and 99mTc-HM-PAO SPECTs was as same as that reported previously by X-CT; beginning at the temporal lobe with eventually being spread to the occipital and frontal lobe. Furthermore, it was shown that findings of both SPECTs could reflect considerably the clinical features, and the laboratory data in central spinal fluid. Thus, 123I-IMP and 99mTc-HM-PAO SPECTs seemed to be a useful tool in the diagnosis, deciding of whether the treatment was suspended or continued, and clarifying the pathophysiology in HSE.