To determine the influence of tumor cell proliferation and changes in the genetic program in malignant cells on the fluorodeoxyglucose (FDG) uptake we performed PET studies in several animal tumors: spontaneous mammary fibroadenoma, chemically-induced mammary adenocarcinoma and Dunning prostate adenocarcinoma. The expression of the glucose transporter (GLUT1) and of hexokinase (Hk) was measured using 32P-labeled cDNA probes and densitometry. Furthermore the proliferative activity was determined with one-dimensional flow cytometry. The FDG uptake and the proliferation parameters were not correlated. The normalized amounts of GLUT and Hk mRNA were lower in spontaneous fibroadenomas and prostate tumors than in chemically induced mammary. The FDG uptake was correlated to GLUT1 expression with r = 0.83 and to Hk expression with r = 0.77. Multiple regression analysis revealed a relation of FDG uptake to GLUT1 and HK with r = 0.87. Our results show that the FDG uptake in our study was related not to differences in proliferation, but rather to differences in the transcription of glycolysis associated genes.