The uptake, distribution, and clearance properties of 123I-IMP in the brain were evaluated in controls and asymptomatic crack users to investigate cerebral blood flow alterations in crack abuse. Serial dynamic planar images of the brain (0-25 min), SPECT of the brain (0.5 hr and 4 hr) and whole-body scans (75 min) were obtained in 21 crack abusers and 21 control subjects. Major observations include: (a) foci of abnormally reduced 123I-IMP activity mainly in the frontal and parieto-occipital cortex or marked irregularities in the uptake of 123I-IMP throughout the cerebral cortex consistent with moderate to severe disruption in regional cerebral blood flow were observed on the 0.5 hr SPECT images of 16/21 asymptomatic crack users; (b) no correlation could be demonstrated between the incidence or severity of SPECT perfusion abnormality with the frequency, amount or length of time of crack use; (c) focal perfusion defects observed in 6/21 crack users on the 0.5-hr SPECT images partially or completely filled-in on delayed SPECT at 4 hr in four of six subjects; (d) the rate of cerebral uptake of 123I-IMP in crack users averaged 23% less than observed in control subjects over the first 25 min after tracer administration; and (e) 123I-IMP activity reaching the brain of cigarette smoking control subjects (n = 14) at 25 min after injection averaged 42.5% less than in nonsmoking controls (n = 7). Quantitative measurements of the uptake and distribution properties of 123I-IMP in the brain proved to be an objective, sensitive and useful measure of regional cerebral blood flow in crack abuse.