The genetics of the effects of nicotine on the open field activity of mice were studied using a 5 by 5 diallel cross. The five inbred strains used were: A, BALB, C57BL, DBA, and C3H. These strains differ both in basal open field activity as well as activity after injection of nicotine. Analysis of the results of baseline activity indicated that both additive and dominance variance affected the activity of the animals. The dominance was non-directional. Likewise, the responses observed after injection of 0.75 mg/kg nicotine displayed both additive and dominance components. However, after correcting the results for differences in basal activity, the dominance item was primarily directional. This directional dominance was towards a more intense response to the effects of the drug, that is, a decrease in open field activity.