We examined possible genetic contributions to MK-801-elicited "popping" behavior in mice. MK-801-elicited "popping" behavior may represent a preclinical screening paradigm for identifying novel antipsychotic medications. Specifically, we studied the sensitivity of four inbred strains of mice (BALB/c, C57BL/6, AKR, and DBA/2) to MK-801-elicited "popping" behavior and compared their response to the outbred NIH Swiss strain in which the behavior was first characterized. The BALB/c strain was most sensitive to the elicitation of MK-801 induced popping behavior, whereas the other inbred strains were less sensitive than the outbred strain. The identification of strain differences in MK-801-elicited "popping" behavior suggests an important role for genetic factors in the elicitation of MK-801 "popping" behavior in mice.