Drug and toxicant effects on locomotor/exploratory activity can be quite variable depending on the test and the schedule of exposure. In neurobehavioral toxicology and teratology, these interactions can affect the inferences based on the use of selected drugs as probes to assess which regulatory mechanisms are affected by one or the other treatment. The present experiments were aimed at comparing morphine effects in CD-1 mice under three conditions, namely, Varimex apparatus (VAR), toggle floor box (TOGGLE), videotape recording (VIDEO) in a home cage environment. Morphine HCI (0, 10, 33, or 100 mg/kg) was given IP 20 min before the start of a 30-min test session. The same procedure was repeated 24 h later. Results of VAR and TOGGLE tests were: dose 10 was largely ineffective; dose 33 induced depression in VAR and hyperactivity in TOGGLE; dose 100 enhanced activity in TOGGLE. There were no differences between session 1 and 2. VIDEO: Univariate analysis results showed that morphine produced a dose-dependent depression of Rearing and Grooming, and an enhancement of Crossing, again without changes due to repeated exposure. Results of Principal Component Analysis supported a response competition model of the changes observed in the mouse behavioral profile. The videorecording (VIDEO) procedure is the one providing the most accurate picture of changes in locomotor/exploratory activity and drug effects thereon, also allowing a more comprehensive statistical analysis of the relationships between various types of response changes.