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Single-photon emission tomographic (SPET) imaging with the radiotracer [123I]2ß-carbomethoxy-3ß-(4-iodophenyl)tropane ([123I]ß-CIT) has been reported to be a useful in vivo measure of dopamine (DA) transporters. However, in addition to its high DA transporter affinity,ß-CIT also binds with high affinity to serotonin (5-HT) transporters. 2ß-Carboisopropoxy-3ß-(4-iodophenyl)tropane (IPCIT) has been demonstrated by in vitro studies to have higher selectivity for the DA transporter. We compared [123I]ß-CIT and [123I]IPCIT SPET imaging and plasma metabolite analyses in baboons to evaluate the potential advantages of [123I]IPCIT for quantitative in vivo measurements of DA transporter densities. Both tracers had low levels (2% of total plasma123I activity) of lipophilic radiolabeled metabolites at 420 min. [123I]IPCIT had significantly higher binding to plasma proteins. The average percent free (nonprotein bound) [123I]ß-CIT and [123I]IPCIT were 52%±7% and 14%±6%, respectively. Region of interest uptake data were normalized by injected dose and body weight. Consistent with the high density of 5-HT transporters in the midbrain and the lower 5-HT transporter affinity of IPCIT, the normalized peak specific midbrain uptake of [123I]ß-CIT (1.7±0.5) was higher than that of [123I]IPCIT (0.4±0.2). Consistent with its greater lipophilicity, [123I]IPCIT had higher nonspecific uptake, such that normalized cerebellar uptake of [123I]IPCIT was about twice that of [123I]ß-CIT. The ratio of specific to nonspecific uptake in striatum was greater for [123I]ß-CIT compared to [123I]IPCIT; however, striatal binding potentials and distribution volumes were not significantly different. In conclusion, [123I]IPCIT demonstrated in vivo a higher DA transporter selectivity and higher level of nonspecific uptake.