Brown adipose tissue (BAT) is a highly thermogenic organ and thermogenesis can be stimulated in cultured BAT with caffeine and RO 20-1724 in combination with a neurotransmitter norepinephrine (NE). Caffeine and RO 20-1724 are well known phoshphodiesterase inhibitors which stimulate UCP1 gene expression in BAT. Stimulation of BAT by 1 μM of caffeine and 0.25 mM of RO 20-1724 shows very little UCP1 mRNA expression and cyclic AMP (cAMP) production in comparison to 0.1 μM of NE. However, addition of NE in the presence of these compounds, the UCP1 mRNA expression and cAMP production increase significantly (becomes more than double) in comparison to the effect of NE alone. This study indicates that the thermogenic effect of NE may be increased significantly after inhibition of phosphodiesterase activity wit caffeine and RO 20-1724.