Approach and avoidance are critical components of novelty seeking, which plays an important role in susceptibility to drug abuse and aspects of cognition. This experiment was designed to examine whether brief periods of handling or prior exposure to a novel environment affect various measures of novel object exploration in mice. Forty male C57BL/6J mice were handled by the experimenter or received minimal exposure to human contact. In addition to manipulating the degree of familiarity with the experimenter (handling), we also manipulated the degree of familiarity with the object. All mice were tested over a 3-day period. On day 1, all mice were tested in the open field for 60min. On day 2, there were two, 30-min sessions. In the first 30-min session, there was no object present. In the second 30-min session, half of the mice were exposed to a novel object. On day 3, all mice were placed in the open field for 30min followed by a 30-min period in which the object was placed in the center of the open field. Handled mice showed a trend toward more object exploration on day 2 compared to non-handled mice. Mice with prior exposure to the novel object showed more object exploration compared to object-naïve mice on day 3. These results are consistent with the hypothesis that a certain degree of familiarity with the object or with the experimenter decreases avoidance and increases exploration of novel stimuli. In combination, these results show that the approach and avoidance dimensions of novelty seeking can be manipulated experimentally and may be used in subsequent studies to examine the effects of drugs of abuse.