C57BL/6J (B6) and DBA2/J (D2) mice differ markedly in voluntary consumption of tastants and responses to abused drugs. In particular, compared to D2 mice, B6 mice avidly drink ethanol and sucrose solutions, but avoid quinine solutions. In the first study, we compared taste reactivity in B6 and D2 mice to determine the extent to which differences in drinking patterns depend on orosensory processing. Both strains showed concentration-dependent increases in positive reactions to sucrose (0.01 to 1 M). Quinine (0.03 to 3 mM) elicited concentration-dependent aversive reactions in B6 mice, whereas all reactions to quinine were virtually indistinguishable from reactions to water in D2 mice. In contrast, D2 mice reacted with relatively strong aversive responses to ethanol (5 to 30%). In the second study, we evaluated the effect of subcutaneous morphine (1 to 4 mg/kg) and methamphetamine (0.5 to 2 mg/kg) on taste reactivity to sucrose. Morphine generally decreased reactions to sucrose in both strains, suggesting a general motor depressant effect. Methamphetamine shifted sucrose responses towards aversion in both strains; particularly in D2 mice. These results suggest that strain-dependent differences in voluntary ethanol and quinine drinking depend at least partially on differences in orosensory responses. However, differences in voluntary sucrose intake may relate solely to genetic differences in post-ingestive factors. Finally, as has been suggested by previous place conditioning studies, methamphetamine appears to induce a dysphoric state in D2 mice, which may be reflected in fewer positive and more negative taste reactions to sucrose in the current study.