We recently conducted an experiment to investigate the possible cooperation between genetic makeup and differential housing on cocaine self-administration in male and female C57BL/6J and DBA/2J mice. Cocaine self-selection was measured in a two-choice test with one choice being cocaine-HCl solution of 40 mg% in tap water and the other choice being plain tap water. Housing conditions began at weaning (21-23 days of age) and consisted of group housed (GH) with 2-3 mice per cage, and isolated housed (IH) with 1 mouse per cage. The results of this study revealed overall strain, sex and housing differences, with C57BL/6Js consuming more cocaine solution than DBA/2J subjects, females consuming more cocaine solution than males, and group housed consuming more than isolate housed subjects. In a second study, the effect of differential housing on open-field locomotor activity was investigated. Testing was conducted on two consecutive days, with subjects receiving an IP injection of saline on day 1, and 15 mg/kg cocaine HCl on day 2. Four behaviors were recorded, including: total distance, nosepokes, stereotypy, and margin time. Overall, the results revealed significant strain differences for stereotypy and nosepokes, and males were found to be more activated by cocaine than females. Additionally, DBA males tended to be differentially affected by housing condition, with IH showing suppressed locomotor activity as compared to GH subjects. Last, significant strain by housing interactions occurred in nosepokes and stereotypy time.