The diagnostic potential of positron emission tomography (PET) with carbon-11 metomidate in patients with adrenocortical cancer (ACC) was evaluated. Thirteen PET examinations were performed in 11 patients with CT-detected primary tumours or recurrence and/or metastases from a previously histopathologically proven ACC. The findings at PET were compared with those at CT and verified by histopathology. Six studies (group A) were performed in patients who at the time of imaging were free of medication that could interfere with 11beta-hydroxylase activity and thereby tracer uptake at PET, such as adrenal steroid inhibitors or chemotherapy. The remaining seven studies (group B) were carried out in patients who were monitored during treatment with one or a combination of these drugs. PET visualised all viable tumours with high tracer uptake, and revealed two more lesions than were seen on CT. Three necrotic tumours were detected as false negative observations, as confirmed at surgery and histopathological examination. A true negative observation was obtained at PET in the case of a suspected liver metastasis on CT that was found to have fat vacuolation at histopathological examination of an ultrasonically guided core biopsy specimen. Group A showed apparently higher uptake in normal tissues than group B (adrenal, P=0.03; liver, P=0.01). The metomidate uptake was increased in tumour lesions as compared with normal tissues (adrenal, P=0.02; liver, P=0.005). ACC could be clearly visualised with (11)C-metomidate PET except when the tumour was necrotic. Medication with adrenal steroid inhibitors and chemotherapy decreased the tracer uptake.