Positron emission tomography (PET) studies have indicated that alteration of active transport contributes to increased net amino acid accumulation into human brain tumors. We compared the uptake of 11C-methionine (MET) and the K+ analog 82Rubidium (RUB) in 30 patients suffering from various brain tumors using PET. MET and RUB accumulated rapidly in tumor tissue and remained on average at a stable level thereafter from which normalized uptake values calculated (tissue radioactivity over injected radioactivity x body weight (NU). K1 (RUB) and K1, k2, k3 (MET) were also estimated using non-linear rate constant fitting in 17/30 patients. NU and K1 values for MET and RUB were higher in meningiomas compared to gliomas and were significantly correlated for the whole spectrum of tumors (p < 0.0001). When meningiomas were excluded, the correlation was maintained. K3 values for MET (metabolic rate) in tumors were in the range of normal brain. No correlation between RUB and MET was found for normal brain. with increasing rub intake the ratio of Nu MET over Nu RUB approached the value of 1.0. These results suggest that apart from active transport, also passive diffusion across the blood-brain barrier (BBB) may account for MET uptake from blood into tumor tissue. This probably limits the use of MET in the differential diagnosis of brain lesions where BBB disruption is present.