Unpredictable environmental conditions and highly fluctuating population densities are believed to have produced a ‘reversed island syndrome’ (RIS) in an insular population of the Wall lizard on Licosa Islet, Italy. Several of the physiological, behavioural, and life-history changes that constitute the RIS could result from positive selection on increased activity of melanocortins. For example, increased levels of α-melanocyte-stimulating hormone (MSH) should lead to increased investment in reproduction and increased immunocompetence in the island population. We tested the crucial assumption of this idea that plasma levels of α-MSH in Licosa Islet lizards are elevated compared to those of the mainland relatives. We also tested for differences in reproductive effort between populations, by measuring plasma levels of 5-α-dihydrotestosterone in males and clutch mass in females. In addition, we assessed ectoparasite load as an indicator for the lizards’ resistance to environmental stress. In agreement with the RIS, we found that insular lizards exhibit higher α-MSH levels, allocate more energy to reproduction, and have a reduced ectoparasite load compared to the nearest mainland population. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, ●●, ●●–●●.