The preference for sweet solutions in opioid receptor-deficient (CXBK) and control (C57BL/6By) mice was compared. CXBK and C57BL/6By (C57) mice were presented for 2 h/day with 2 tubes, one always containing water and the other containing either water or various concentrations of saccharin solution. Fifteen minutes before the drinking session, half of the mice in each strain were injected with naltrexone (0.2 mg/kg) and the other half with saline. Compared to C57 mice, CXBK mice had significantly lower saccharin preference. Naltrexone reduced the saccharin preference in both strains, almost completely abolishing preference in CXBK mice. The results support the hypothesis that brain opioid receptors are involved in mediating sweet palatability and suggest that genetic differences in opioid receptor density contribute to differences in the palatability of sweet solutions.