Male mice with a null mutation of Mchr1, encoding melanin concentrating hormone receptor-1, were compared to wild-type on two background strains. Mchr1 knockout (KO) mice were more active than 129/SvEv and C57BL/6J wild-type strains in a photocell actimeter. In addition, Mchr1 KO mice on the C57BL/6J background were less anxious in the elevated plus-maze, while on the 129/SvEv background, the mutants were less emotionally reactive as estimated by fecal boli and handling-related vocalization. There was no detrimental impact of the null mutation on motor coordination and spatial learning. Mchr1 KO mice had shorter latencies before reaching the escape platform, but only on the 129/SvEv background. Null mutants were lighter than C57BL/6J controls but heavier than 129/SvEv controls, attributable to interactions with strain-dependent genes.