Single photon emission computed tomography (SPECT) is being increasingly used as an adjunctive technique in the localisation of epileptogenic foci prior to surgery. Fourteen patients (five male, nine female; mean age 31 years) with refractory complex partial seizures, all of whom had abnormal 99Tc HM-PAO SPECT scans, were imaged again using the benzodiazepine receptor ligand 123I-iomazenil. Eleven of these patients displayed the same abnormality on both scans. The magnitude of the deficit, however, was slightly greater (P < 0.05) on the iomazenil scan compared with the HM-PAO study. These 11 patients were then randomised into two groups. Group 1 (n = 7) received clobazam 20 mg/day for a minimum of 7 days before a second iomazenil study was performed. Patients in group 2 (n = 4) underwent a second iomazenil scan at the same time interval as those in group 1, but without the additional clobazam. The resultant scans were reported blind to treatment. There were no qualitative or quantitative differences between the first and second iomazenil studies in either group. Patients can be imaged using 123I-iomazenil without withdrawing clobazam therapy. From this preliminary study, there seems little advantage in using iomazenil in place of HM-PAO to delineate the extent of the zone of epileptogenesis. Whether iomazenil SPECT will prove to be more sensitive in identifying the site of the epileptic focus remains to be determined.