The pharmacokinetics and quality of planar and SPECT brain imaging of two 99mTc-labeled brain perfusion agents, d,l-hexamethyl propylene amine oxime (HMPAO) and ethyl cysteinate dimer (ECD), were compared in seven healthy, normal subjects. Both radiopharmaceuticals showed rapid brain uptake and had a net brain washout of less than 5% during the first 20 min after drug administration. However, during the same time period, 99mTc-ECD images of the head showed significantly less background facial uptake and retention when compared to 99mTc-HMPAO images. The brain-to-background contrast ratio of 99mTc-ECD (brain/neck) continued to improve over time and by 5 hr postadministration was 17 to 1 versus 2 to 1 for 99mTc-HMPAO. SPECT brain images of both agents show gray/white matter ratios that were unchanged over time and an intracerebral distribution consistent with blood flow. A blind read of these SPECT images also shows 99mTc-ECD to produce images that were "easier to interpret" with less extracerebral activity as compared to 99mTc-HMPAO. Repeat, whole-body planar spot imaging suggests that 99mTc-ECD was cleared more rapidly from the body than was 99mTc-HMPAO.