Background: Intraveneous (i.v) PYY3-36 infusions have been reported to reduce energy intake (EI) in humans, whereas few studies exist on effects of PYY1-36. The aim of the present study was to examine effects of subcutaneous (s.c.) injections of PYY1-36 and PYY3-36 on appetite, ad libitum EI, plasma concentrations of PYY and free fatty acids (FFA) in obese males. Method: Twenty-four males (BMI: 27-40 kg/m²) were randomly assigned to 2 groups receiving s.c. injections of either PYY1-36 or PYY3-36 in a blinded, placebo-controlled, dose-escalating, cross-over study. Subjects were studied 5 days in succession, with escalating doses of PYY1-36 (saline, 50, 100, 150, and 200 pmol PYY1-36/kg lean body mass (LBM)), or PYY3-36 (saline, 25, 50, 75, and 100 pmol PYY3-36/kg LBM), respectively. Results: PYY injections resulted in dose-dependent increases in plasma PYY levels but no effect on EI in either the PYY1-36 or the PYY3-36 group. However, increasing doses of PYY3-36, but not PYY1-36, resulted in increased ratings of satiety and decreased ratings of hunger, thirst and prospective food consumption. Although not dose dependent significant elevation of plasma FFA was seen after injection of PYY3-36, but not PYY1-36. Conclusion: Although s.c. administration of PYY was well-tolerated it remains to be determined if high dose PYY3-36 is sufficient in reducing EI in long term trials and if so, if the reduction in EI occurs without nausea. PYY1-36 is unlikely to be important in regulating energy intake. The PYY3-36 administrations caused a non-dose dependent mobilisation of FFA, likely through a direct effect.