Mutant mice lacking the RIIβ subunit of protein kinase A (regulatory subunit II beta−/−) show increased ethanol preference. Recent evidence suggests a relationship between heightened ethanol preference and susceptibility to ethanol-induced locomotor sensitization. It is currently unknown if protein kinase A signaling modulates the stimulant effects and/or behavioral sensitization caused by ethanol administration. To address this question, we examined the effects of repeated ethanol administration on locomotor activity RIIβ−/− and littermate wild-type (RIIβ+/+) mice on multiple genetic backgrounds.