Common features shared by addictive drugs have been difficult to identify. One ubiquitous effect of these drugs is psychomotor stimulation. Further, repeated exposure commonly results in sensitization to drug stimulant effects. This study evaluates sensitization to drugs from several drug classes in C57BL/6J and DBA/2J inbred strain mice. DBA/2J mice showed sensitized responses to ethanol and methamphetamine, whereas C57BL/6J mice developed sensitization to morphine and methamphetamine. Strain susceptibilities to ethanol- and morphine-induced sensitization closely paralleled their sensitivities to the acute stimulant effects of these drugs; this was not the case for methamphetamine. The relative sensitivities of DBA/2J and C57BL/6J mice were not consistent across drugs, suggesting that the stimulant and sensitized responses to these drugs may be mediated by at least partially divergent neural mechanisms.